Arrays and methods comprising m. smithii gene products

ABSTRACT

The present invention encompasses arrays and methods related to the genome of  Methanobrevibacter - smithii.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the priority of PCT application PCT/US2008/065344, filed May 30, 2008, which claims the priority of U.S. provisional application No. 60/932,457, filed May 31, 2007, each of which is hereby incorporated by reference in its entirety.

GOVERNMENTAL RIGHTS

This invention was made with government support under Grant numbers DK30292 and DK70077 awarded by the National Institutes of Health. The government has certain rights in the invention.

FIELD OF THE INVENTION

The present invention encompasses arrays and methods related to the genome of Methanobrevibacter smithii.

BACKGROUND OF THE INVENTION I. Weight Problems and Current Approaches

According to the Center for Disease Control (CDC), over sixty percent of the United States population is overweight, and almost twenty percent are obese. This translates into 38.8 million adults in the United States with a Body Mass Index (BMI) of 30 or above. Obesity is also a world-wide health problem with an estimated 500 million overweight adult humans [body mass index (BMI) of 25.0-29.9 kg/m²] and 250 million obese adults. This epidemic of obesity is leading to worldwide increases in the prevalence of obesity-related disorders, such as diabetes, hypertension, as well as cardiac pathology, and non-alcoholic fatty liver disease (NAFLD).

According to the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) approximately 280,000 deaths annually are directly related to obesity. The NIDDK further estimated that the direct cost of healthcare in the U.S. associated with obesity is $51 billion. In addition, Americans spend $33 billion per year on weight loss products. In spite of this economic cost and consumer commitment, the prevalence of obesity continues to rise at alarming rates. From 1991 to 2000, obesity in the U.S. grew by 61%.

Additionally, malnourishment or disease may lead to individuals being under weight. The World Health Organization estimates that one-third of the world is under-fed and one-third is starving. Over 4 million will die this year from malnourishment. One in twelve people worldwide is malnourished, including 160 million children under the age of 5.

II. Gastrointestinal Microbiota

Humans are host to a diverse and dynamic population of microbial symbionts, with the majority residing within the distal intestine. The gut microbiota contains representatives from ten known divisions of the domain Bacteria, with an estimated 500-1000 species-level phylogenetic types present in a given healthy adult human; the microbiota is dominated by members of two divisions of Bacteria, the Bacteroidetes and the Firmicutes. Members of the domain Archaea are also represented, most prominently by a methanogenic Euryarchaeote, Methanobrevibacter smithii and occasionally Methanosphaera stadtmanae. The density of colonization increases by eight orders of magnitude from the proximal small intestine (10³) to the colon (10¹¹). The distal intestine is an anoxic bioreactor whose microbial constituents help the subject by providing a number of key functions: e.g., breakdown of otherwise indigestible plant polysaccharides and regulating subject storage of the extracted energy; biotransformation of conjugated bile acids and xenobiotics; degradation of dietary oxalates; synthesis of essential vitamins; and education of the immune system.

Dietary fiber is a key source of nutrients for the microbiota. Monosaccharides are absorbed in the proximal intestine, leaving dietary fiber that has escaped digestion (e.g. resistant starches, fructans, cellulose, hemicelluloses, pectins) as the primary carbon sources for microbial members of the distal gut. Fermentation of these polysaccharides yields short-chain fatty acids (SCFAs; mainly acetate, butyrate and propionate) and gases (H₂ and CO₂). These end products benefit humans. For example, SCFAs are an important source of energy, as they are readily absorbed from the gut lumen and are subsequently metabolized in the colonic mucosa, liver, and a variety of peripheral tissues (e.g., muscle). SCFAs also stimulate colonic blood flow and the uptake of electrolytes and water.

III. Methanogens

Methanogens are members of the domain Archaea. Methanogens thrive in many anaerobic environments together with fermentative bacteria. These habitats include natural wetlands as well as man-made environments, such as sewage digesters, landfills, and bioreactors. Hydrogen-consuming, mesophilic methanogens are also present in the intestinal tracts of many invertebrate and vertebrate species, including termites, birds, cows, and humans. Using methane breath tests, clinical studies estimate that between 30 and 80 percent of humans harbor methanogens.

Culture- and non-culture-based enumeration studies have demonstrated that members of the Methanobrevibacter genus are prominent gut mesophilic methanogens. The most comprehensive enumeration of the adult human colonic microbiota reported to date found a single predominant archaeal species, Methanobrevibacter smithii. This gram-positive-staining Euryarchaeote can comprise up to 10¹⁰ cells/g feces in healthy humans, or ˜10% of all anaerobes in the colons of healthy adults.

A focused set of nutrients are consumed for energy by methanogens: primarily H₂/CO₂, formate, acetate, but also methanol, ethanol, methylated sulfur compounds, methylated amines and pyruvate. These compounds are typically converted to CO₂ and methane (e.g. acetate) or reduced with H₂ to methane alone (e.g. methanol or CO₂). Some methanogens are restricted to utilizing only H₂/CO₂ (e.g. Methanobrevibacter arbophilicus), or methanol (e.g. Methanospaera stadtmanae). Other more ubiquitous methanogens exhibit greater metabolic diversity, like Methanosarcina species. In vitro studies suggest that M. smithii is intermediate in this metabolic spectrum, consuming H₂/CO₂ and formate as energy sources.

IV. Anaerobic Microbial Fermentation in the Mammalian Intestine

Fermentation of dietary fiber is accomplished by syntrophic interactions between microbes linked in a metabolic food web, and is a major energy-producing pathway for members of the Bacteroidetes and the Firmicutes. Bacteroides thetaiotaomicron has previously been used as a model bacterial symbiont for a variety of reasons: (i) it effectively ferments a range of otherwise indigestible plant polysaccharides in the human colon; (ii) it is genetically manipulatable; and, (iii) it is a predominant member of the human distal intestinal microbiota. Its 6.26 Mb genome has been sequenced: the results reveal that B. thetaiotaomicron has a large collection of known or predicted glycoside hydrolases (261 in total; by comparison, our human genome only encodes 99 known or predicted glycoside hydrolases). B. thetaiotaomicron also has a significant expansion of outer membrane polysaccharide binding and importing proteins (over 208 paralogs of two starch binding proteins known as SusC and SusD), as well as a large repertoire of environmental sensing proteins [e.g. 50 extra-cytoplasmic function (ECF)-type sigma factors; 25 anti-sigma factors, and 32 novel hybrid two-component systems]. Functional genomics studies of B. thetaiotaomicron in vitro and in the ceca of gnotobiotic mice, indicates that it is capable of very flexible foraging for dietary (and host-derived) polysaccharides, allowing this organism to have a broad niche and contributing to the functional stability of the microbiota in the face of changes in the diet.

In vitro biochemical studies of B. thetaiotaomicron and closely related Bacteroides species (B. fragilis and B. succinogenes) indicate that their major end products of fermentation are acetate, succinate, H₂ and CO₂. Small amounts of pyruvate, formate, lactate and propionate are also formed.

V. Removal of Hydrogen from the Intestinal Ecosystem is Important for Efficient Microbial Fermentation

Anaerobic fermentation of sugars causes flux through glycolytic pathways, leading to accumulation of NADH (via glyceraldehyde-3P dehydrogenase) and the reduced form of ferredoxin (via pyruvate:ferredoxin oxidoreductase). B. thetaiotaomicron is able to couple NAD⁺ recovery to reduction of pyruvate to succinate (via malate dehydrogenase and fumarase reductase), or lactate (via lactate dehydrogenase). Oxidation of reduced ferredoxin is easily coupled to production of H₂. However, H₂ formation is, in principle, not energetically feasible at high partial pressures of the gas. In other words, lower partial pressures of H₂ (1-10 Pa) allow for more complete oxidation of carbohydrate substrates. The subject removes some hydrogen from the colon by excretion of the gas in the breath and as flatus. However, the primary mechanism for eliminating hydrogen is by interspecies transfer from bacteria by hydrogenotrophic methanogens. Formate and acetate can also be transferred between some species, but their transfer is complicated by their limited diffusion across the lipophilic membranes of the producer and consumer. In areas of high microbial density or aggregation like in the gut, interspecies transfer of hydrogen, formate and acetate is likely to increase with decreasing physical distance between microbes.

Methanogen-mediated removal of hydrogen can have a profound impact on bacterial metabolism. Not only does re-oxidation of NADH occur, but end products of fermentation undergo a shift from a mixture of acetate, formate, H₂, CO₂, succinate and other organic acids to predominantly acetate and methane with small amounts of succinate. This facilitates disposal of reducing equivalents, and produces a potential gain in ATP production due to increased acetate levels. For example, a reduction in hydrogen allows Clostridium butyricum to acquire 0.7 more ATP equivalents from fermentation of hexose sugars. Co-culture of M. smithii with a prominent cellulolytic ruminal bacterial species, Fibrobacter succinogenes S85, results in augmented fermentation, as manifested by increases in the rate of ATP production and organic acid concentrations. Co-culture of M. smithii association with Ruminococcus albus eliminates NADH-dependent ethanol production from acetyl-CoA, thereby skewing bacterial metabolism towards production of acetate, which is more energy yielding. H₂-producing fibrolytic bacterial strains from the human colon exhibit distinct cellulose degradation phenotypes when co-cultured with M. smithii, indicating that some bacteria are more responsive to syntrophy with methanogens.

While there is suggestive evidence that methanogens cooperate metabolically with members of Bacteroides, studies have not elucidated the impact of this relationship on a subject's energy storage or on the specificity and efficiency of carbohydrate metabolism. Colonization of adult germ-free mice with M. smithii and/or B. thetaiotaomicron, revealed that the methanogen increased the efficiency and changed the specificity of bacterial digestion of dietary glycans. Moreover, co-colonized mice exhibited a significantly greater increase in adiposity compared with mice colonized with either organism alone.

SUMMARY OF THE INVENTION

One aspect of the present invention encompasses an array. The array comprises a substrate having disposed thereon at least one nucleic add, wherein the nucleic acid comprises a nucleic acid sequence selected from the nucleic acid sequences listed in Table A.

Another aspect of the present invention encompasses an array. The array comprises a substrate having disposed thereon at least one polypeptide, wherein the polypeptide is encoded by a nucleic acid sequence selected from the nucleic acid sequences listed in Table A.

Yet another aspect of the present invention encompasses a method of selecting a compound that has efficacy for modulating a gene product of M. smithii present in the gastrointestinal tract of a subject. The method comprises comparing an M. smithii gene profile to a gene profile of the subject, identifying a gene product of the M. smithii gene profile that is divergent from a corresponding gene product of the subject gene profile, or absent in the gene profile of the subject, and selecting a compound that modulates the M. smithii gene product but does not substantially modulate the corresponding divergent gene product of the subject.

Still another aspect of the invention encompasses a method for modulating a gene product of M. smithii present in the gastrointestinal tract of a subject. The method comprises administering to the subject an HMG-CoA reductase inhibitor. The inhibitor may be formulated for release in the distal portion of the subject's gastrointestinal tract and thereby substantial inhibit more of the HMG-CoA reductase of M. smithii compared to the subject's HMG-CoA reductase.

Other aspects and iterations of the invention are described more thoroughly below.

REFERENCE TO COLOR FIGURES

The application file contains at least one photograph executed in color. Copies of this patent application publication with color photographs will be provided by the Office upon request and payment of the necessary fee.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1. depicts a micrograph and a graph illustrating that M. smithii produces glycans that mimic those produced by humans—(A) TEM of M. smithii harvested from the ceca of adult GF mice after a 14 day colonization. The inset shows a comparable study of stationary phase M. smithii recovered from a batch fermentor containing Methanobrevibacter complex medium (MBC). Note that the size of the capsule is greater in cells recovered from the cecum (open vs. closed arrow). (B) Comparison of glycosyltransferase (GT), glycosylhydrolase (GH) and carbohydrate esterase (CE) families (defined in CAZy; Table 10) represented in the genomes of the following sequenced methanogens (see Table 5): Msm, Methanobrevibacter smithii; Msp, Methanosphaera stadtmanae; Mth, Methanothermobacter thermoautotrophicus; Mac, Methanosarcina acetivorans; Mba, M. barkeri; Mma, M. mazei; Mmp, Methanococcus maripaludis; Mja, M. jannaschii; Mhu, Methanospirillum hungatei; Mbu, Methanococcoides burtonii; and Mka, Methanopyrus kandleri. Gut methanogens (highlighted in orange) have no GH or CE family members, but have a larger proportion of family 2 GTs (^(ψ), p<0.00005 based on binomial test for enrichment vs. non-gut associated methanogens). Scale bar, 100 μm in panel A.

FIG. 2. depicts graphs and diagrams illustrating biochemical assays of M. smithii metabolism in the ceca of gnotobiotic mice. (A) In silico metabolic reconstructions of M. smithii pathways involved in (i) methanogenesis from formate, H₂/CO₂, and alcohols, (ii) carbon assimilation from acetate and bicarbonate, and (iii) nitrogen assimilation from ammonium. Abbreviations: Acs, acetyl-CoA synthase; Adh, alcohol dehydrogenase; Ags, 18α-ketoglutarate synthase; AmtB, ammonium transporter; BtcA/B, bicarbonate (HCO₃) ABC transporter; Cab, carbonic anhydrase; CH₃, methyl; CoA, coenzyme A; CoB, coenzyme B; CoM, coenzyme M; COR, corrinoid; F₄₂₀, cofactor F₄₂₀; F₄₃₀, cofactor F₄₃₀; Fd, ferredoxin (ox-oxidized, red-reduced); FdhAB, formate dehydrogenase subunits; FdhC, formate transporter; Fno, F₄₂₀-dependent NADP reductase; Ftr, formylmethanofuran:tetrahydromethanopterin (H₄MPT) formyltransferase; Fum, fumarate hydratase; Fwd, tungsten formylmethanofuran dehydrogenase; GdhA, glutamate dehydrogenase; GlnA, glutamine synthetase; GltA/B, glutamate synthase subunits A and B; Hmd, H₂-forming methylene-H₄MPT dehydrogenase; Kor, 2-oxoglutarate synthase; Mch, methenyl-H₄MPT cyclohydrolase; Mcr, methyl-CoM reductase; Mdh, malate dehydrogenase; MeOH, methanol; Mer, methylene-H₄MPT reductase; MFN, methanofuran; MtaB, methanol:cobalamin methyltransferase; Mtd, F₄₂₀-dependent methylene-H₄MPT dehydrogenase; Mtr, methyl-H₄ MPT:CoM methyltransferase; NH4, ammonium; OA, oxaloacetate; PEP, phosphoenol pyruvate; Por, pyruvate:ferredoxin oxidoreductase; Pps, phosphoenolpyruvate synthase; PRPP, 5-phospho-a-D-ribosyl-1-pyrophosphate; Pyc, pyruvate carboxylase; RfaS, ribofuranosylaminobenzene 5′-phosphate (RFA-P) synthase; Sdh, succinate dehydrogenase; Suc, succinyl-CoA synthetase. (B) Ethanol (EtOH) levels in the ceca of mice colonized with B. thetaiotaomicron±M. smithii (n=10-15 animals/group representing 3 independent experiments; each sample assayed in duplicate; mean values±SEM plotted). (C) Ratio of cecal concentrations of glutamine (Gln) and 2-oxoglutarate (2-OG) (n=5 animals/group; samples assayed in duplicate; mean values±SEM). (D) Cecal levels of free Gln (glutamine), Glu (glutamate) and Asn (asparagine) (n=5 animals/group; samples assayed in duplicate; mean values±SEM). (E) Cecal ammonium and urea levels measured in samples used for the assays shown in panels C and D. *, p<0.05; **, p<0.01; ***, p<0.005, according to Student's t-test.

FIG. 3. depicts a diagram of the analysis of the M. smithii pan-genome. Schematic depiction of the conservation of M. smithii PS genes [depicted in the outermost circle where the color code is orange for forward strand ORFs (F) and blue for reverse strand ORFs (R)] in (i) other M. smithii strains (GeneChip-based genotyping of strains F1, ALI, and B181; circles in increasingly lighter shades of green, respectively), (ii) the fecal microbiomes of two healthy individuals [human gut microbiome (HGM), shown as the red plot in the fifth innermost circle with nucleotide identity plotted from 80% (closest to the purple circle) to 100% (closest to lightest green ring); see also FIG. 9 for details], and (iii) two other members of the Methanobacteriales division, M. stadtmanae (Msp; purple circle), another human gut methanogen, and M. thermoautotrophicus (Mth; yellow circle), an environmental thermophile [mutual best blastp hits (e-value <10⁻²⁰)]. Tick marks in the center of the Figure indicate nucleotide number in kbps. Asterisks denote the positions of ribosomal rRNA operons. Letters highlight distinguishing features among M. smithii genomes: the table below the figure summarizes differences in M. smithii gene content between strains F1, ALI, and B181 as well as the two human fecal metagenomic datasets.

FIG. 4. depicts two illustrations of the analysis of synteny between M. smithii and M. stadtmanae genomes. (A) Dot plot comparison. (B) Results obtained with the Artemis Comparison Tool (Carver et al., (2005) Bioinformatics 21:3422-3) set to tBLASTX and the most stringent confidence level (blue, forward strand; orange, reverse strand). The gut methanogens exhibit limited synteny.

FIG. 5. depicts an illustration of the predicted interaction network of M. smithii clusters of orthologous groups (COGs) based on STRING. Individual M. smithii COGs are represented by nodes (circles; 622 of the 1352 COGs in M. smithii's genome). Predicted interactions are represented by black lines (0.95 confidence interval; summary of 9,765 total predicted interactions are shown). COG conservation among the Methanobacteriales is denoted by node color: red, M. smithii alone; yellow, gut methanogens; green, M. smithii and M. thermoautotrophicus; and gray, all three genomes. Several clusters are highlighted: (A) molybdopterin biosynthesis (methanogenesis from CO₂); (B) ion transport; (C) DNA repair/recombination; (D) antimicrobial transport; (E) sialic acid synthesis; (F) amino acid transport system; (G) HMG-CoA reductase cluster; and (H) conserved archaeal membrane protein cluster. See Table 9 for lists of genes assigned to COGs.

FIG. 6. depicts an illustration, a graph, and a micrograph showing sialic acid production by M. smithii in vitro. (A) M. smithii gene cluster (MSM1535-40) encoding enzymes predicted to be needed to synthesize sialic acid-like sugars (N-acetylneuraminic acid; Neu5Ac): CapD, polysaccharide biosynthesis protein/sugar epimerase; DegT, pleiotropic regulatory protein/amidotransferase; NeuS, Neu5Ac cytidylyltransferase; NeuA, CMP-Neu5Ac synthetase; NeuB, Neu5Ac synthase; Gpd, glycerol-3-phosphate dehydrogenase. (B) Reverse phase-HPLC of derivatized M. smithii cell wall extracts. The position of elution of N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) standards are shown. The concentration of Neu5Ac species of sialic acid, as defined by co-elution with standards, in M. smithii cell walls, when the organism has been cultured in a batch fermentor for 6 d in supplemented MBC medium (does not contain any sialic acid sources), is 410 pmol/g wet weight of cells (average of three assays). (C) Lectin staining with fluorescein-labeled SNA (Sambucus nigra agglutinin) shows that M. smithii F1 is decorated with Neu5Ac epitopes (counter stained with DAPI; ×100 magnification). The specificity of lectin staining was assessed using E. coli K92 (positive control; sialic acid-producing), B. longum NCC2705 (negative control) and M. smithii cells with no lectin added (background autofluorescence control).

FIG. 7. depicts distinct complements of adhesin-like proteins in gut methanogens. A maximum likelihood tree of a CLUSTALW alignment of all adhesin-like proteins (ALPs) in M. smithii (47; red branches) and in M. stadtmanae (38; black branches). Each methanogen possesses specific clades of ALPs. Branches that are supported by bootstrap values >70% are noted. InterPro-based analysis reveals that many of these proteins contain common adhesin domains [i.e., invasin/intimin domains (IPR008964) and pectate lyase folds (IPR011050)]. They also have domains associated with additional functionality (basis for branch highlighting): (i) sugar binding [e.g., galactose-binding-like (IPR008979) and Concanavalin A-like lectin (IPR013320)]; (ii) glycosaminoglycan (GAG)-binding (IPR012333); or (iii) peptidase activity [e.g., carboxypeptidase regulatory region (IPR008969) and beta-lactamase/transpeptidase-like fold (IPR012338)]; (iv) transglycosidase activity [e.g., glycosidase superfamily domains (SSF51445)]; and/or (v) general adhesin/porin activity [e.g., Bacillus anthracis OMP repeats/DUF11 (IPR001434)]. See Table 11 for a complete list of ALPs and domains identified by InterProScan.

FIG. 8. depicts an illustration showing the importance of the molybdopterin biosynthesis pathway for methanogenesis from carbon dioxide in M. smithii. (A) In silico metabolic reconstruction of the predicted molybdopterin biosynthesis pathway encoded by the M. smithii genome. Molybdopterin can chelate molybdate (MoO₄ ⁻) or tungstate (WO₄ ²⁻) ions. Abbreviations: MoaABCE, molybdenum cofactor biosynthesis proteins A (MSM0849, MSM1406), B (MSM0840), C (MSM1362), and E (MSM0130); MoeAB, molybdopterin biosynthesis proteins A (MSM1343) and B (MSM0729); ModABC, molybdate ABC transport system (MSM1609-11); MobAB, molybdopterin-guanine dinucleotide (MGD) biosynthesis proteins A (MSM0240) and B (MSM1407); PP, pyrophosphate. Note that the molybdate transporter may also be used for WO₄ ²⁻, as no dedicated complex has been identified for its transport. (B) Schematic of the first step in the methanogenesis pathway from carbon dioxide (CO₂) catalyzed by tungsten-containing formylmethanofuran dehydrogenase (Fwd; MSM1408-14, MSM0783, MSM1396). Essential cofactors for this reaction include tungsten delivered by MGD, methanofuran (MFN), and ferridoxin [Fd; converted from a reduced (red) to oxidized (ox) form during the reaction].

FIG. 9. illustrates the divergence in genes involved in surface variation, genome evolution, and metabolism among M. smithii strains and in the human gut microbiomes of two healthy adults. Each of the 139,521 unidirectional reads in the metagenomic dataset (Gill et al., (2006) Science 312, 1355-9) were compared to the M. smithii PS genome using NUCmer. Reads with nucleotide sequence identity ≧80% (present) are plotted. A summary of representation of M. smithii PS genes present in the metagenomic dataset is displayed at the bottom of the graph (92% of the total ORFs). [Note that the gaps are indications of genome plasticity in the dataset, and include transposases, restriction-modification systems and prophage genes.] Selected regions of heterogeneity (divergence) are highlighted; genes in these regions are involved in the metabolism of bacterial products, recombination/repair machinery (Recomb), anti-microbial resistance (AntiMicrob), surface variation (Surface), and adhesion (ALPs). See Table 2 for details.

FIG. 10 depicts three graphs showing the dose effect of atorvastatin (A), pravastatin (B), and rosuvastatin (C) on M. smithii strain PS.

FIG. 11 depicts three graphs showing the dose effect of atorvastatin (A), pravastatin (B), and rosuvastatin (C) on M. smithii strain F1.

FIG. 12 depicts three graphs showing the dose effect of atorvastatin (A), pravastatin (B), and rosuvastatin (C) on M. smithii strain ALI.

FIG. 13 depicts three graphs showing the dose effect of atorvastatin (A), pravastatin (B), and rosuvastatin (C) on M. smithii strain B181.

FIG. 14 depicts three graphs showing the effect of statins (concentration of 1 mM) on B. thetaiotaomicron.

FIG. 15 depicts two photographs of the PHAT system described in the Examples. Panel A shows the pressurized incubation vessels within the anaerobic chamber, while Panel B shows an individual PHAT system outside of the chamber.

DETAILED DESCRIPTION

The present invention provides arrays and methods utilizing the genome and proteome of the methanogen M. smithii, which is the predominant methanogen present in the human gastrointestinal tract. Modulating the Archaeal population of the gastrointestinal tract of a subject, of which M. smithii is a major component, modulates the efficiency and selectivity of carbohydrate metabolism. The genome and proteome of M. smithii may be used, according to the methods presented herein, to promote weight loss or weight gain in a subject. In particular, the methods of the present invention may be used to identify compounds that promote weight loss or weight gain in a subject. The method relies on applicants' discovery that certain M. smithii gene products are conserved between M. smithii strains, yet divergent (or absent) from the correlating gene products expressed by the subject's microbiome or genome. This allows the selection of compounds that specifically modulate the M. smithii gene product, while substantially not modulating the subject's gene product.

I. Arrays

One aspect of the invention encompasses use of biomolecules in an array. As used herein, biomolecule refers to either nucleic acids derived from the M. smithii genome, or polypeptides derived from the M. smithii proteome. The M. smithii genome or proteome may be utilized to construct arrays that may be used for several applications, including discovery of compounds that modulate one or more M. smithii gene products, judging efficacy of existing weight gain or loss regimes, and for the identification of biomarkers involved in weight gain or loss, or a weight gain or loss related disorder.

The array may be comprised of a substrate having disposed thereon at least one biomolecule. Several substrates suitable for the construction of arrays are known in the art. The substrate may be a material that may be modified to contain discrete individual sites appropriate for the attachment or association of the biomolecule and is amenable to at least one detection method. Alternatively, the substrate may be a material that may be modified for the bulk attachment or association of the biomolecule and is amenable to at least one detection method. Non-limiting examples of substrate materials include glass, modified or functionalized glass, plastics (including acrylics, polystyrene and copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, TeflonJ, etc.), nylon or nitrocellulose, polysaccharides, nylon, resins, silica or silica-based materials including silicon and modified silicon, carbon, metals, inorganic glasses and plastics. In an exemplary embodiment, the substrates may allow optical detection without appreciably fluorescing.

A substrate may be planar, a substrate may be a well, i.e. a 1534-, 384-, or 96-well plate, or alternatively, a substrate may be a bead. Additionally, the substrate may be the inner surface of a tube for flow-through sample analysis to minimize sample volume. Similarly, the substrate may be flexible, such as a flexible foam, including closed cell foams made of particular plastics. Other suitable substrates are known in the art.

The biomolecule or biomolecules may be attached to the substrate in a wide variety of ways, as will be appreciated by those in the art. The biomolecule may either be synthesized first, with subsequent attachment to the substrate, or may be directly synthesized on the substrate. The substrate and the biomolecule may both be derivatized with chemical functional groups for subsequent attachment of the two. For example, the substrate may be derivatized with a chemical functional group including, but not limited to, amino groups, carboxyl groups, oxo groups or thiol groups. Using these functional groups, the biomolecule may be attached using functional groups on the biomolecule either directly or indirectly using linkers.

The biomolecule may also be attached to the substrate non-covalently. For example, a biotinylated biomolecule can be prepared, which may bind to surfaces covalently coated with streptavidin, resulting in attachment. Alternatively, a biomolecule or biomolecules may be synthesized on the surface using techniques such as photopolymerization and photolithography. Additional methods of attaching biomolecules to arrays and methods of synthesizing biomolecules on substrates are well known in the art, i.e. VLSIPS technology from Affymetrix (e.g., see U.S. Pat. No. 6,566,495, and Rockett and Dix, Xenobiotica 30(2):155-177, each of which is hereby incorporated by reference in its entirety).

In one embodiment, the biomolecule or biomolecules attached to the substrate are located at a spatially defined address of the array. Arrays may comprise from about 1 to about several hundred thousand addresses. In one embodiment, the array may be comprised of less than 10,000 addresses. In another alternative embodiment, the array may be comprised of at least 10,000 addresses. In yet another alternative embodiment, the array may be comprised of less than 5,000 addresses. In still another alternative embodiment, the array may be comprised of at least 5,000 addresses. In a further embodiment, the array may be comprised of less than 500 addresses. In yet a further embodiment, the array may be comprised of at least 500 addresses.

A biomolecule may be represented more than once on a given array. In other words, more than one address of an array may be comprised of the same biomolecule. In some embodiments, two, three, or more than three addresses of the array may be comprised of the same biomolecule. In certain embodiments, the array may comprise control biomolecules and/or control addresses. The controls may be internal controls, positive controls, negative controls, or background controls.

The biomolecule may be a nucleic acid derived from the M. smithii genome (GenBank Accession number CP000678), comprising, in part, nucleic acid sequences labeled MSM001 through MSM1795, inclusive. Such nucleic acids may include RNA (including mRNA, tRNA, and rRNA), DNA, and naturally occurring or synthetically created derivatives. A nucleic acid derived from the M. smithii genome is a nucleic acid that comprises at least a portion of a nucleic acid sequence selected from the nucleic acid sequences listed in Table A. The nucleic acid may comprise fewer than 10, at least 10, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 150, at least 200, or more than 200 bases of a nucleic acid sequence selected from the nucleic acid sequences listed in Table A. One embodiment of the invention is an array comprising a substrate, the substrate having disposed thereon at least one nucleic acid, wherein the nucleic acid comprises a nucleic acid sequence selected from the nucleic acid sequences listed in Table A. In another embodiment, the nucleic acid consists of a nucleic acid sequence selected from the nucleic acid sequences listed in Table A. In certain embodiments, the nucleic acid comprises a nucleic acid sequence derived from a sequence in Table A marked by an asterick. The asterick marks sequences associated with a core gut-associated M. smithii genome.

In one embodiment, the nucleic acid or nucleic acids may be selected from the group of nucleic acids listed in Table A that are conserved among M. smithii strains, but divergent from a corresponding nucleic acid of the subject. In this context, a “corresponding nucleic acid” refers to a nucleic acid sequence of the subject, or the subject's micobiome, that has greater than 75% identity to a nucleic acid sequence of Table A. The term, “divergent,” as used herein, refers to a sequence of Table A that has less than 99% identity, but greater than 75% identity, with a nucleic acid sequence of the subject, or the subject's microbiome. For instance, in some embodiments, divergent refers to less than or equal to about 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, 90%, 89%, 88%, 87%, 86%, 85%, 84%, 83%, 82%, 81%, 80%, 79%, 78%, 77%, or 76%, identity between the nucleic acid sequence of Table A and the nucleic acid sequence of the subject. Conversely, the term “conserved,” as used herein, refers to a nucleic acid sequence of one M. smithii strain that has greater than about 90% identity to a nucleic acid sequence from another M. smithii strain.

If a subject, or the subject's microbiome, does not comprise a nucleic acid sequence that has greater than 75% identity to a nucleic acid sequence of Table A, that nucleic acid sequence of Table A is “absent” from the subject. In certain embodiments, the nucleic acid or nucleic acids of the array of the invention are selected from the group comprising nucleic acid sequences that are absent from the subject gut microbiome or genome. For instance, in one embodiment, the nucleic acid may be selected from the group of nucleic acids designated absent or divergent in Table 2. Percent identity may be determined as discussed below.

Alternatively, the nucleic acid or nucleic acids derived from the M. smithii genome (Table A) may be selected from the group of nucleic acids comprising nucleic acid sequences that are expressed in vivo by M. smithii while residing in the gastrointestinal tract of a subject. In another embodiment, the nucleic acid or nucleic acids may be selected from the group of nucleic acids comprising nucleic acid sequences that are expressed by M. smithii while residing in the gastrointestinal tract of a subject, and whose expression levels are not affected by the presence of actively fermenting bacteria. In another embodiment, the nucleic acid or nucleic acids may be selected from the group of nucleic acids comprising nucleic acid sequences that are expressed by M. smithii while residing in the gastrointestinal tract of a subject, and whose expression levels are affected by the presence of actively fermenting bacteria. The in vivo expression levels of a nucleic acid may be determined by methods known in the art, including RT-PCR. In yet another embodiment, the nucleic acid or nucleic acids may be selected from the group of nucleic acids that encode the M. smithii transcriptome or metabolome.

The biomolecule may also be a polypeptide derived from the M. smithii proteome. A polypeptide derived from the M. smithii proteome is a polypeptide that is encoded by at least a portion of a nucleic acid sequence selected from the nucleic acid sequences listed in Table A. The polypeptide may comprise fewer than 10, at least 10, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 150, at least 200, or more than 200 amino acids encoded by a nucleic acid sequence selected from the nucleic acid sequences listed in Table A. One embodiment of the invention is an array comprising a substrate, the substrate having disposed thereon at least one polypeptide, wherein the polypeptide is encoded by a nucleic acid sequence selected from the nucleic acid sequences listed in Table A. In certain embodiments, a biomolecule may be an amino acid sequence derived from a sequence in Table A marked by an asterick. The asterick marks sequences associated with a core gut-associated M. smithii genome.

In one embodiment, the polypeptide or polypeptides may be selected from the group of polypeptides comprising polypeptide sequences that are conserved among M. smithii strains, but divergent from a corresponding polypeptide of the subject. The terms conserved and divergent are used as defined above. In certain embodiments, the polypeptide or polypeptides are selected from the group comprising polypeptides absent from the subject gut microbiome or genome. In another embodiment, the polypeptide or polypeptides may be selected from the group of polypeptides comprising polypeptide sequences with greater than about 75% but less than about 99% identity to a correlating polypeptide from the subject gut microbiome or genome. In yet another embodiment, the polypeptide or polypeptides may be selected from the group of polypeptides comprising polypeptide sequence with greater than about 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% identity to a correlating polypeptide from the subject gut microbiome or genome. In one embodiment, for instance, the polypeptide may be encoded by a nucleic acid designated absent or divergent in Table 2. Percent identity may be determined as discussed below.

Alternatively, the polypeptide or polypeptides derived from the M. smithii proteome (see Table A) may be encoded by a nucleic acid selected from the group of nucleic acids comprising nucleic acid sequences that are expressed in vivo by M. smithii while residing in the gastrointestinal tract of a subject. In another embodiment, the polypeptide or polypeptides may be encoded by a nucleic acid selected from the group of nucleic acids comprising nucleic acid sequences that are expressed by M. smithii while residing in the gastrointestinal tract of a subject, and whose expression levels are not affected by the presence of actively fermenting bacteria. In still another embodiment, the polypeptide or polypeptides may be encoded by a nucleic acid selected from the group of nucleic acids comprising nucleic acid sequences that are expressed by M. smithii while residing in the gastrointestinal tract of a subject, and whose expression levels are affected by the presence of actively fermenting bacteria. In yet another embodiment, the polypeptide or polypeptides may be encoded by a nucleic acid selected from the group of nucleic acids that encode the M. smithii transcriptome or metabolome.

The array may alternatively be comprised of biomolecules from the genome or proteome of M. smithii that are indicative of an obese subject microbiome. Alternatively, the array may be comprised of biomolecules from the genome or proteome of M. smithii that are indicative of a lean subject microbiome. A biomolecule is “indicative” of an obese or lean microbiome if it tends to appear more often in one type of microbiome compared to the other. Such differences may be quantified using commonly known statistical measures, such as binomial tests. An “indicative” biomolecule may be referred to as a “biomarker.”

Additionally, the array may be comprised of biomolecules from the genome or proteome of M. smithii that are modulated in the obese subject microbiome compared to the lean subject microbiome. As used herein, “modulated” may refer to a biomolecule whose representation or activity is different in an obese subject microbiome compared to a lean subject microbiome. For instance, modulated may refer to a biomolecule that is enriched, depleted, up-regulated, down-regulated, degraded, or stabilized in the obese subject microbiome compared to a lean subject microbiome. In one embodiment, the array may be comprised of a biomolecule enriched in the obese subject microbiome compared to the lean subject microbiome. In another embodiment, the array may be comprised of a biomolecule depleted in the obese subject microbiome compared to the lean subject microbiome. In yet another embodiment, the array may be comprised of a biomolecule up-regulated in the obese subject microbiome compared to the lean subject microbiome. In still another embodiment, the array may be comprised of a biomolecule down-regulated in the obese subject microbiome compared to the lean subject microbiome. In still yet another embodiment, the array may be comprised of a biomolecule degraded in the obese subject microbiome compared to the lean subject microbiome. In an alternative embodiment, the array may be comprised of a biomolecule stabilized in the obese subject microbiome compared to the lean subject microbiome.

Additionally, the biomolecule may be at least 80, 85, 90, or 95% homologous to a biomolecule derived from Table A. In one embodiment, the biomolecule may be at least 80, 81, 82, 83, 84, 85, 86, 87, 88, or 89% homologous to a biomolecule derived from Table A. In another embodiment, the biomolecule may be at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% homologous to a biomolecule derived from Table A.

In certain embodiments, an array of the invention may comprise at least one, ten, a hundred, or a thousand different sequences listed in Table A, or amino acid sequences derived from the sequences listed in Table A. For instance, an array may comprise about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800, 810, 820, 830, 840, 850, 860, 870, 880, 890, 900, 910, 920, 930, 940, 950, 960, 970, 980, 990, 1000, 1010, 1020, 1030, 1040, 1050, 1060, 1070, 1080, 1090, 1100, 1110, 1120, 1130, 1140, 1150, 1160, 1170, 1180, 1190, 1200, 1210, 1220, 1230, 1240, 1250, 1260, 1270, 1280, 1290, 1300, 1310, 1320, 1330, 1340, 1350, 1360, 1370, 1380, 1390, 1400, 1410, 1420, 1430, 1440, 1450, 1460, 1470, 1480, 1490, 1500, 1510, 1520, 1530, 1540, 1550, 1560, 1570, 1580, 1590, 1600, 1610, 1620, 1630, 1640, 1650, 1660, 1670, 1680, 1690, 1700, 1710, 1720, 1730, 1740, 1750, 1760, 1770, 1780, 1790, or about 1800 different nucleic acid sequences listed in Table A or amino acids derived from the sequences listed in Table A.

In determining whether a biomolecule is substantially homologous or shares a certain percentage of sequence identity with a sequence of the invention, sequence similarity may be determined by conventional algorithms, which typically allow introduction of a small number of gaps in order to achieve the best fit. In particular, “percent identity” of two polypeptides or two nucleic acid sequences is determined using the algorithm of Karlin and Altschul (Proc. Natl. Acad. Sci. USA 87:2264-2268, 1993). Such an algorithm is incorporated into the BLASTN and BLASTX programs of Altschul et al. (J. Mol. Biol. 215:403-410, 1990). BLAST nucleotide searches may be performed with the BLASTN program to obtain nucleotide sequences homologous to a nucleic acid molecule of the invention. Equally, BLAST protein searches may be performed with the BLASTX program to obtain amino acid sequences that are homologous to a polypeptide of the invention. To obtain gapped alignments for comparison purposes, Gapped BLAST is utilized as described in Altschul et al. (Nucleic Acids Res. 25:3389-3402, 1997). When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., BLASTX and BLASTN) are employed. See http://www.ncbi.nlm.nih.gov for more details.

Furthermore, the biomolecules used for the array may be labeled. One skilled in the art understands that the type of label selected depends in part on how the array is being used. Suitable labels may include fluorescent labels, chromagraphic labels, chemi-luminescent labels, FRET labels, etc. Such labels are well known in the art.

II. Use of the Arrays

The arrays may be utilized in several suitable applications. For example, the arrays may be used in methods for detecting association between a biomolecule of the array and a compound in a sample. In this context, compound refers to a nucleic acid, a protein, a lipid, or chemical compound. In some embodiments, a compound may be an antibody. This method typically comprises incubating a sample with the array under conditions such that the compounds comprising the sample may associate with the biomolecules attached to the array. The association is then detected, using means commonly known in the art, such as fluorescence. “Association,” as used in this context, may refer to hybridization, covalent binding, ionic binding, hydrogen binding, van der Waals binding, and dated binding. A skilled artisan will appreciate that conditions under which association may occur will vary depending on the biomolecules, the compounds, the substrate, and the detection method utilized. As such, suitable conditions may have to be optimized for each individual array created.

In one embodiment, the array may be used as a tool in methods to determine whether a compound has efficacy for modulating a gene product of M. smithii. In certain embodiments, the array may be used as a tool in methods to determine whether a compound has efficacy for modulating a gene product of M. smithii while M. smithii is residing in the gastrointestinal tract of a subject. Typically, such a method comprises comparing a plurality of biomolecules from either the M. smithii genome or proteome before and after administration of a compound for modulating a gene product of M. smithii, such that if the abundance of a biomolecule that correlates with the gene product is modulated, the compound is efficacious in modulating a gene product of M. smithii. The array may also be used to quantitate the plurality of biomolecule's of M. smithii's genome or proteome before and after administration of a compound. The abundance of each biomolecule in the plurality may then be compared to determine if there is a decrease in the abundance of biomolecules associated with the compound. In other embodiments, the array may be used to quantify the levels of M. smithii in an obese subject prior to, during, or after treatment for obesity. Alternatively, the array may be used to quantify the levels of M. smithii in an underfed individual prior to, during, or after implementation of dietary recommendations designed to increase nutrient and energy harvest.

In a further embodiment, the array may be used as a tool in methods to determine whether a compound has efficacy for treatment of weight gain or a weight gain related disorder in a subject. Typically, such a method comprises comparing a plurality of biomolecules of M. smithii's genome or proteome before and after administration of a compound for the treatment of weight gain or a weight gain related disorder, such that if the abundance of biomolecules associated with weight gain decreased after treatment, the compound is efficacious in treating weight gain in a subject.

In still a further embodiment, the array may be used as a tool in methods to determine whether a compound has efficacy for treatment of weight loss or a weight loss related disorder in a subject. Typically, such a method comprises comparing a plurality of biomolecules of M. smithii's genome or proteome before and after administration of a compound for the treatment of weight loss or a weight loss related disorder, such that if the abundance of biomolecules associated with weight loss decreased after treatment, the compound is efficacious in treating weight loss in a subject.

In an alternative embodiment, a proteome array of the invention may be used to screen antibodies that bind to one or more sequences of the M. smithii proteome.

The present invention also encompasses M. smithii gene profiles. Generally speaking, a gene profile is comprised of a plurality of values with each value representing the abundance of a biomolecule derived from either the M. smithii genome or proteome. The abundance of a biomolecule may be determined, for instance, by sequencing the nucleic acids of the M. smithii genome as detailed in the examples. This sequencing data may then be analyzed by known software to determine the abundance of a biomolecule in the analyzed sample. An M. smithii gene profile may comprise biomolecules from more than one M. smithii strain. The abundance of a biomolecule may also be determined using an array described above. For instance, by detecting the association between compounds comprising an M. smithii derived sample and the biomolecules comprising the array, the abundance of M. smithii biomolecules in the sample may be determined.

A profile may be digitally-encoded on a computer-readable medium. The term “computer-readable medium” as used herein refers to any medium that participates in providing instructions to a processor for execution. Such a medium may take many forms, including but not limited to non-volatile media, volatile media, and transmission media. Non-volatile media may include, for example, optical or magnetic disks. Volatile media may include dynamic memory. Transmission media may include coaxial cables, copper wire and fiber optics. Transmission media may also take the form of acoustic, optical, or electromagnetic waves, such as those generated during radio frequency (RF) and infrared (IR) data communications. Common forms of computer-readable media include, for example, a floppy disk, a flexible disk, hard disk, magnetic tape, or other magnetic medium, a CD-ROM, CDRW, DVD, or other optical medium, punch cards, paper tape, optical mark sheets, or other physical medium with patterns of holes or other optically recognizable indicia, a RAM, a PROM, and EPROM, a FLASH-EPROM, or other memory chip or cartridge, a carrier wave, or other medium from which a computer can read.

A particular profile may be coupled with additional data about that profile on a computer readable medium. For instance, a profile may be coupled with data about what therapeutics, compounds, or drugs may be efficacious for that profile. Conversely, a profile may be coupled with data about what therapeutics, compounds, or drugs may not be efficacious for that profile. Alternatively, a profile may be coupled with known risks associated with that profile. Non-limiting examples of the type of risks that might be coupled with a profile include disease or disorder risks associated with a profile. The computer readable medium may also comprise a database of at least two distinct profiles.

Profiles may be stored on a computer-readable medium such that software known in the art and detailed in the examples may be used to compare more than one profile.

Another aspect of the invention is a method for selecting a compound that has efficacy for modulating a gene product of M. smithii present in the gastrointestinal tract of a subject. The method generally comprises comparing an M. smithii gene profile to a gene profile of the subject and identifying a gene product of the M. smithii gene profile that is divergent from a corresponding gene product of the subject gene profile, or absent in the gene profile of the subject. Next the method comprises selecting a compound that modulates the M. smithii gene product, but does not substantially modulate the corresponding gene product of the subject. In a further embodiment, the compound also does not substantially modulate the corresponding gene product of an archaeon other than M. smithii, or a non-archaeal microbe, in the gastrointestinal tract of the subject. The compound may for instance, inhibit or promote the growth of M. smithii. The compound may also decrease or increase the efficiency of carbohydrate metabolism in the subject. Accordingly, the compound may also promote weight loss or weight gain in the subject.

Another further aspect of the invention is a method for selecting a compound that has efficacy for modulating a gene product of M. smithii present in the gastrointestinal tract of a subject. The method comprises comparing an M. smithii gene profile to a gene profile of the subject and identifying a gene product of the M. smithii gene profile that is divergent from a corresponding gene product of the subject gene profile, or absent in the gene profile of the subject. Next the method comprises selecting a compound that can be administered so as to modulate the M. smithii gene product, but not substantially modulate the corresponding gene product of the subject. In a further embodiment, the administered compound also does not substantially modulate the corresponding gene product of an archaeon other than M. smithii, or a non-archaeal microbe, in the gastrointestinal tract of the subject. The compound may be administered, for instance, so as to inhibit or promote the growth of M. smithii. The compound may also be administered so as to decrease or increase the efficiency of carbohydrate metabolism in the subject. Accordingly, the compound may also be administered so as to promote weight loss or weight gain in the subject.

The present invention also encompasses a kit for evaluating a compound, therapeutic, or drug. Typically, the kit comprises an array and a computer-readable medium. The array may comprise a substrate having disposed thereon at least one biomolecule that is derived from the M. smithii genome or proteome. In some embodiments, the array may comprise at least one biomolecule that is derived from the M. smithii metabolome or transcriptome. The computer-readable medium may have a plurality of digitally-encoded profiles wherein each profile of the plurality has a plurality of values, each value representing the abundance of a biomolecule derived from M. smithii detected by the array. The array may be used to determine a profile for a particular subject under particular conditions, and then the computer-readable medium may be used to determine if the profile is similar to known profile stored on the computer-readable medium. Non-limiting examples of possible known profiles include obese and lean profiles for several different subjects.

III. Method of Promoting Weight Loss or Gain

A further aspect of the invention encompasses a method of promoting weight loss or gain. The method incorporates the discovery that modulating the Archaeon population of the gastrointestinal tract of a subject, of which M. smithii is a major component, modulates the efficiency and selectivity of carbohydrate metabolism. Furthermore, the method relies on applicants' discovery that certain M. smithii gene products are conserved among M. smithii strains, yet divergent (or absent) from the correlating gene products expressed by the subject's microbiome or genome. This divergence allows the selection of compounds to specifically modulate the M. smithii gene product, while substantially not modulating the subject's gene product, as described above.

By way of non-limiting example, weight loss may be promoted by administering an HMG-CoA reductase inhibitor to a subject. In an exemplary embodiment, the inhibitor will selectively inhibit the HMG-CoA reductase expressed by M. smithii and not the HMG-CoA reductase expressed by the subject. In another embodiment, a second HMG CoA-reductase inhibitor may be administered that selectively inhibits the HMG CoA-reductase expressed by the subject in lieu of the HMG-CoA reductase expressed by M. smithii. In yet another embodiment, an HMG-CoA reductase inhibitor that selectively inhibits the HMG-CoA reductase expressed by the subject may be administered in combination with an HMG-CoA reductase inhibitor that selectively inhibits the HMG-CoA reductase expressed by M. smithii. One means that may be utilized to achieve such selectivity is via the use of time-release formulations as discussed below. Compounds that inhibit HMG-CoA reductase are well known in the art. For instance, non-limiting examples include atorvastatin, pravastatin, rosuvastatin, and other statins.

(a) Pharmaceutical Compositions

These compounds, for example HMG-CoA reductase inhibitors, may be formulated into pharmaceutical compositions and administered to subjects to promote weight loss. According to the present invention, a pharmaceutical composition includes, but is not limited to, pharmaceutically acceptable salts, esters, salts of such esters, or any other adduct or derivative which upon administration to a subject in need is capable of providing, directly or indirectly, a composition as otherwise described herein, or a metabolite or residue thereof, e.g., a prodrug.

The pharmaceutical compositions maybe administered by several different means that will deliver a therapeutically effective dose. Such compositions can be administered orally, parenterally, by inhalation spray, rectally, intradermally, intracisternally, intraperitoneally, transdermally, bucally, as an oral or nasal spray, or topically (i.e. powders, ointments or drops) in dosage unit formulations containing conventional nontoxic pharmaceutically acceptable carriers, adjuvants, and vehicles as desired. Topical administration may also involve the use of transdermal administration such as transdermal patches or iontophoresis devices. The term parenteral as used herein includes subcutaneous, intravenous, intramuscular, or intrasternal injection, or infusion techniques. In an exemplary embodiment, the pharmaceutical composition will be administered in an oral dosage form. Formulation of drugs is discussed in, for example, Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa. (1975), and Liberman, H. A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y. (1980).

The amount of an HMG-CoA reductase inhibitor that constitutes an “effective amount” can and will vary. The amount will depend upon a variety of factors, including whether the administration is in single or multiple doses, and individual subject parameters including age, physical condition, size, and weight. Those skilled in the art will appreciate that dosages may also be determined with guidance from Goodman & Goldman's The Pharmacological Basis of Therapeutics, Ninth Edition (1996), Appendix II, pp. 1707-1711 and from Goodman & Goldman's The Pharmacological Basis of Therapeutics, Tenth Edition (2001), Appendix II, pp. 475-493.

(b) Controlled Release Formulations

As described above, an HMG-CoA reductase inhibitor may be specific for the M. smithii enzyme, or for the subject's enzyme, depending, in part, on the selectivity of the particular inhibitor and the area the inhibitor is targeted for release in the subject. For example, an inhibitor may be targeted for release in the upper portion of the gastrointestinal tract of a subject to substantially inhibit the subject's enzyme. In contrast, the inhibitor may be targeted for release in the lower portion of the gastrointestinal tract of a subject, i.e., where M. smithii resides, then the inhibitor may substantially inhibit M. smithii's enzyme.

In order to selectively control the release of an inhibitor to a particular region of the gastrointestinal tract for release, the pharmaceutical compositions of the invention may be manufactured into one or several dosage forms for the controlled, sustained or timed release of one or more of the ingredients. In this context, typically one or more of the ingredients forming the pharmaceutical composition is microencapsulated or dry coated prior to being formulated into one of the above forms. By varying the amount and type of coating and its thickness, the timing and location of release of a given ingredient or several ingredients (in either the same dosage form, such as a multi-layered capsule, or different dosage forms) may be varied.

The coating can and will vary depending upon a variety of factors, including, the particular ingredient, and the purpose to be achieved by its encapsulation (e.g., time release). The coating material may be a biopolymer, a semi-synthetic polymer, or a mixture thereof. The microcapsule may comprise one coating layer or many coating layers, of which the layers may be of the same material or different materials. In one embodiment, the coating material may comprise a polysaccharide or a mixture of saccharides and glycoproteins extracted from a plant, fungus, or microbe. Non-limiting examples include corn starch, wheat starch, potato starch, tapioca starch, cellulose, hemicellulose, dextrans, maltodextrin, cyclodextrins, inulins, pectin, mannans, gum arabic, locust bean gum, mesquite gum, guar gum, gum karaya, gum ghatti, tragacanth gum, funori, carrageenans, agar, alginates, chitosans, or gellan gum. In another embodiment, the coating material may comprise a protein. Suitable proteins include, but are not limited to, gelatin, casein, collagen, whey proteins, soy proteins, rice protein, and corn proteins. In an alternate embodiment, the coating material may comprise a fat or oil, and in particular, a high temperature melting fat or oil. The fat or oil may be hydrogenated or partially hydrogenated, and preferably is derived from a plant. The fat or oil may comprise glycerides, free fatty acids, fatty acid esters, or a mixture thereof. In still another embodiment, the coating material may comprise an edible wax. Edible waxes may be derived from animals, insects, or plants. Non-limiting examples include beeswax, lanolin, bayberry wax, carnauba wax, and rice bran wax. The coating material may also comprise a mixture of biopolymers. As an example, the coating material may comprise a mixture of a polysaccharide and a fat.

In an exemplary embodiment, the coating may be an enteric coating. The enteric coating generally will provide for controlled release of the ingredient, such that drug release can be accomplished at some generally predictable location in the lower intestinal tract below the point at which drug release would occur without the enteric coating. In certain embodiments, multiple enteric coatings may be utilized. Multiple enteric coatings, in certain embodiments, may be selected to release the ingredient or combination of ingredients at various regions in the lower gastrointestinal tract and at various times.

The enteric coating is typically, although not necessarily, a polymeric material that is pH sensitive. A variety of anionic polymers exhibiting a pH-dependent solubility profile may be suitably used as an enteric coating in the practice of the present invention to achieve delivery of the active to the lower gastrointestinal tract. Suitable enteric coating materials include, but are not limited to: cellulosic polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl cellulose succinate and carboxymethylcellulose sodium; acrylic acid polymers and copolymers, preferably formed from acrylic acid, methacrylic acid, methyl acrylate, ammonio methylacrylate, ethyl acrylate, methyl methacrylate and/or ethyl methacrylate (e.g., those copolymers sold under the trade name “Eudragit”); vinyl polymers and copolymers such as polyvinyl pyrrolidone, polyvinyl acetate, polyvinylacetate phthalate, vinylacetate crotonic acid copolymer, and ethylene-vinyl acetate copolymers; and shellac (purified lac). In one embodiment, the coating may comprise plant polysaccharides that can only be digested in the distal gut by the microbiota. For instance, a coating may comprise pectic galactans, polygalacturonates, arabinogalactans, arabinans, or rhamnogalacturonans. Combinations of different coating materials may also be used to coat a single capsule.

The thickness of a microcapsule coating may be an important factor in some instances. For example, the “coating weight,” or relative amount of coating material per dosage form, generally dictates the time interval between oral ingestion and drug release. As such, a coating utilized for time release of the ingredient or combination of ingredients into the gastrointestinal tract is typically applied to a sufficient thickness such that the entire coating does not dissolve in the gastrointestinal fluids at pH below about 5, but does dissolve at pH about 5 and above. The thickness of the coating is generally optimized to achieve release of the ingredient at approximately the desired time and location.

As will be appreciated by a skilled artisan, the encapsulation or coating method can and will vary depending upon the ingredients used to form the pharmaceutical composition and coating, and the desired physical characteristics of the microcapsules themselves. Additionally, more than one encapsulation method may be employed so as to create a multi-layered microcapsule, or the same encapsulation method may be employed sequentially so as to create a multi-layered microcapsule. Suitable methods of microencapsulation may include spray drying, spinning disk encapsulation (also known as rotational suspension separation encapsulation), supercritical fluid encapsulation, air suspension microencapsulation, fluidized bed encapsulation, spray cooling/chilling (including matrix encapsulation), extrusion encapsulation, centrifugal extrusion, coacervation, alginate beads, liposome encapsulation, inclusion encapsulation, colloidosome encapsulation, sol-gel microencapsulation, and other methods of microencapsulation known in the art. Detailed information concerning materials, equipment and processes for preparing coated dosage forms may be found in Pharmaceutical Dosage Forms: Tablets, eds. Lieberman et al. (New York: Marcel Dekker, Inc., 1989), and in Ansel et al., Pharmaceutical Dosage Forms and Drug Delivery Systems, 6^(th) Ed. (Media, Pa.: Williams & Wilkins, 1995).

DEFINITIONS

The term “activity of the microbiota population” refers to the microbiome's ability to harvest energy.

An “effective amount” is a therapeutically-effective amount that is intended to qualify the amount of agent that will achieve the goal of modulating an M. smithii gene product, promoting weight loss, or promoting weight gain.

As used herein, “gene product” refers to a nucleic acid derived from a particular gene, or a polypeptide derived from a particular gene. For instance, a gene product may be a mRNA, tRNA, rRNA, cDNA, peptide, polypeptide, protein, or metabolite.

“Metabolome” as used herein is defined as the network of enzymes and their substrates and biochemical products, which operate within subject or microbial cells under various physiological conditions.

As used herein, the term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and other subjects without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge, et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 66: 1 19 (1977), incorporated herein by reference. The salts can be prepared in situ during the final isolation and purification of the composition of the invention, or separately by reacting the free base function with a suitable organic acid. Non-limiting examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, hydroionic acid, nitric acid, carbonic acid, phosphoric acid, sulfuric acid and perchloric acid.

As used herein, the “subject” may be, generally speaking, an organism capable of supporting M. smithii in its gastrointestinal tract. For instance, the subject may be a rodent or a human. In one embodiment, the subject may be a rodent, i.e. a mouse, a rat, a guinea pig, etc. In an exemplary embodiment, the subject is human.

“Transcriptome” as used herein is defined as the network of genes that are being actively transcribed into mRNA in subject or microbial cells under various physiological conditions.

The phrase “weight gain related disorder” includes disorders resulting from, at least in part, obesity. Representative disorders include metabolic syndrome, type II diabetes, hypertension, cardiovascular disease, and nonalcoholic fatty liver disease. The phrase “weight loss related disorder” includes disorders resulting from, at least in part, weight loss. Representative disorders include malnutrition and cachexia.

As various changes could be made in the above compounds, products and methods without departing from the scope of the invention, it is intended that all matter contained in the above description and in the examples given below, shall be interpreted as illustrative and not in a limiting sense.

EXAMPLES

The following examples illustrate various iterations of the invention.

Materials and Methods for the Examples Genome Sequencing and Annotation

Methanobrevibacter smithii strain PS (ATCC 35061) was grown as described below for 6 d at 37° C. DNA was recovered from harvested cell pellets using the QIAGEN Genomic DNA Isolation kit with mutanolysin (1 unit/mg wet weight cell pellet; Sigma) added to facilitate lysis of the microbe. An ABI 3730xl instrument was used for paired end-sequencing of inserts in a plasmid library (average insert size 5 Kb; 42,823 reads; 11.6×-fold coverage), and a fosmid library (average insert size of 40 Kb; 7,913 reads; 0.6×-fold coverage). Phrap and PCAP (Huang et al. (2003) Genome Res 13:2164-70) were used to assemble the reads. A primer-walking approach was used to fill-in sequence gaps. Physical gaps and regions of poor quality (as defined by Consed; Gordon et al., (1998) Genome Res. 8, 195-202) were resolved by PCR-based re-sequencing. The assembly's integrity and accuracy was verified by clone constraints. Regions containing insufficient coverage or ambiguous assemblies were resolved by sequencing spanning fosmids. Sequence inversions were identified based on inconsistency of constraints for a fraction of read pairs in those regions. The final assembly consisted of 12.6× sequence coverage with a Phred base quality value 40. Open-reading frames (ORFs) were identified and annotated as described below.

Biochemical Assays

Perchloric acid-, hydrochloric acid-, and alkali extracts of freeze dried cecal contents were prepared, and established pyridine nucleotide-linked microanalytic assays (Passonneau et al., (1993) Enzymatic Analysis:A practical guide) used to measure metabolites.

Microbes and Culturing

All M. smithii strains [PS (ATCC 35061), ALI (DSMZ 2375), B181 (DSMZ 11975), and F1 (DSMZ 2374)] were cultivated in 125 ml serum bottles containing 15 ml MBC medium supplemented with 3 g/L formate, 3 g/L acetate, and 0.3 mL of a freshly prepared anaerobic solution of filter-sterilized 2.5% Na₂S (Samuel et al., (2006) PNAS 103:10011-6). The remaining volume in the bottle (headspace) contained a 4:1 mixture of H₂ and CO₂: the headspace was replenished every 1-2 d for a 6 d growth at 37° C.

M. smithii PS was also cultured in a BioFlor-110 batch fermentor with dual 1.5 L fermentation vessels (New Brunswick Scientific). Each vessel contained 750 ml of supplemented MBC medium. One hour prior to inoculation, 7.5 ml of sterile 2.5% Na₂S solution was added to the vessel, followed by one half of the contents of a serum bottle culture that had been harvested on day 5 of growth. Microbes were then incubated at 37° C. under a constant flow of H₂/CO₂ (4:1) (agitation setting, 250 rpm). One milliliter of a sterile solution of 2.5% Na₂S was added daily.

Colonization of Germ-Free Mice with M. smithii PS with and without B. thetaiotaomicron VPI-5482

Mice belonging to the NMRI/KI inbred strain (Bry et al., (1996) Science 273:1380-3) were housed in gnotobiotic isolators (Hooper et al., (2002) Mol Cell Micro 31:559-589) where they were maintained under a strict 12 h light cycle (lights on at 0600 h) and fed a standard, autoclaved, polysaccharide-rich chow diet (B&K Universal, East Yorkshire, UK) ad libitum. Each mouse was inoculated at age 8 weeks with a single gavage of 10⁸ microbes/strain [B. thetaiotaomicron was harvested from an overnight culture in TYG medium (Sonnenburg et al., Science 307:1955-9); M. smithii from serum bottles containing MBC medium after a 5 d incubation at 37° C. (Samuel et al., (2006) PNAS 103:10011-6)]. For a given experiment, the same preparation of cultured microbes was used for mono-association (single species added) and co-colonization (both species added).

Immediately after animals were sacrificed, cecal contents were recovered for preparation of DNA, RNA and biochemical studies (n=5 mice/treatment group/experiment; n=3 independent experiments). Colonization density was assessed using a qPCR-based assay employing species-specific primers, as described in Samuel et al., (2006) PNAS 103:10011-6.

Genome Annotation

M. smithii genes were identified by comparing outputs from GLIMMER v.3.01 (Delcher et al., (1999) Nucleic Acids Res 27:4636-41), CRITICA v.1.05b (Badger et al., (1999) Mol Biol Evol 16:512-24), and GeneMarkS v.2.1 (Besemer et al. (2001) Nucleic Acids Res 29:2607-18). WUBLAST (http://blast.wustl.edu/) was then used to identify all ORFs with significant hits to the NR database (as of Dec. 1, 2006). ORFs containing <30 codons and without significant homology (e-value threshold of 10⁻⁵) to other proteins, were eliminated. rRNA and tRNA genes were identified using BLASTN and tRNA-Scan (Lowe et al., (1997) Nucleic Acids Res 25:955-64). Annotation of the predicted proteome of M. smithii was completed by using BLAST homology searches against public databases, and domain analysis with Pfam (http://pfam.janelia.org/) and InterProScan [release 12.1; (Apweiler et al., Nucleic Acids Res 29:37-40)]. Functional classifications were made based on GO terms assigned by InterProScan and homology searches against COGs (Tatusov et al., (2001) Nucleic Acids Res 29:22-8), followed by manual curation. Metabolic pathways were constructed based on KEGG (Kanehisa et al., (2004) Nucleic Acids Res 32:D277-80) and MetaCyc [(Caspi et al., (2006) Nucleic Acids Res 34:D511-6); http://metacyc.org/)]. Glycosyltransferases (GT) were categorized according to CAZy [http://www.cazy.org; (Coutinho et al., (1999) Recent Advances in Carbohydrate Bioengineering p. 3-12)]. Putative prophage genes were identified using two independent approaches: (i) BLASTN of predicted M. smithii ORFs against a database of all known phage sequences (http://phage.sdsu.edu/phage); and (ii) Hidden Markov Model (HMM)-based analysis using Phage_Finder (Fouts (2006) Nucleic Acids Res 34:5839-51).

Comparative Genomic Analyses

GO term assignments—The number of genes in each archaeal genome that were assigned to each GO term, or to its parents in the GO hierarchy [version available on Jun. 6, 2006; (Ashburner et al., (2000) Nat Genet 25:25-9)] were totaled. All terms assigned to at least five genes in a given genome were then subjected to statistical tests for overrepresentation, and all terms with a total of five genes across all tested genomes for under-representation, using a binomial comparison reference set (see Table 6). Genes that could not be assigned to a GO category were excluded from the reference sets. A false discovery rate of <0.05 was set for each comparison (Benjamini et al., (1995) J of the Royal Statistical Society B 57:289-300). All tests were implemented using the Math::CDF Perl module (E. Callahan, Environmental Statistics, Fountain City, Wis.; available at http://www.cpan.org/), and scripts written in Perl.

Percent identity comparisons—The M. smithii PS genome sequence was compared to the M. stadtmanae genome (Fricke et al., (2006) J Bacteriol 188:642-58) and a 78 Mb metagenomic dataset of the human fecal microbiome (Gill et al., (2006) Science 312:1355-9) using NUCmer (part of MUMmer v.3.19 package; (Kurtz et al., Genome Biol 5:R12), and a percent identity plot was generated using Mummerplot.

Genomic synteny—Comparisons of synteny between M. smithii and M. stadtmanae were completed using the Artemis Comparison Tool (Carver et al., (2005) Bioinformatics 21:3422-3) set to tBLASTX and the most stringent confidence level.

M. smithii interaction network analyses—All M. smithii COGs were submitted to the STRING database (http://string.embl.de/; (von Mering et al., (2003) Nucleic Acids Res 31:258-61) to create predicted interaction networks (0.95 confidence interval). The program Medusa (Hooper et al., (2005) Bioinformatics 21:4432-3) was then used to organize the networks and color the nodes based on their conservation in M. smithii's proteome (mutual best BLASTP hits with e-values <10⁻²⁰ to the other Methanobacteriales genomes).

Clustering of adhesin-like proteins—M. smithii and M. stadtmanae ALPs were first aligned using CLUSTALW (v.1.83; (Chenna et al., (2003) Nucleic Acids Res 31:3497-500)). To retain the highest level of discrimination between the proteins, the alignment was subsequently converted into a nucleotide alignment using PAL2NAL (Suyama et al., (2006) Nucleic Acids Res 34:W609-12). The resulting alignment was used to create a maximum likelihood tree with RAxML [Randomized accelerated maximum likelihood for high performance computing [RAxML-VI-HPC, v2.2.1; (Stamatakis (2006) Bioinformatics 22:2688-90)] first using the GTR+CAT approximation method for rapid generation of tree topology, followed by the GTR+gamma evolutionary model for determination of likelihood values. ModelTest (v3.7; http://darwin.uvigo.es/software/modeltest.html) also identified GTR+gamma as the most appropriate evolutionary model for the dataset. Bootstrap values were determined from 100 neighbor-joining trees in Paup (v. 4.0b10, http://paup.csit.fsu.edu/). Tree visualization was completed with TreeView (Page (1996) Comput Appl Biosci 12:357-8).

Functional Genomic Analysis of M. smithii Gene Expression in Gnotobiotic Mice

RNA isolation—100-300 mg aliquots of frozen cecal contents from each gnotobiotic mouse was added to 2 ml tubes containing 250 μl of 212-300 μm-diameter acid-washed glass beads (Sigma), 500 μl of buffer A (200 mM NaCl, 20 mM EDTA), 210 μl of 20% SDS, and 500 μl of a mixture of phenol:chloroform:isoamyl alcohol (125:24:1; pH 4.5; Ambion). Samples were lysed using a bead beater (BioSpec; ‘high’ setting for 5 min at room temperature) and cellular debris was pelleted by centrifugation (10,000×g at 4° C. for 3 min). The extraction was repeated by adding another 500 μL of phenol:chloroform:isoamyl alcohol to the aqueous supernatant. RNA was precipitated from the pooled aqueous phases, resuspended in 100 μl nuclease-free water (Ambion), 350 μl Buffer RLT (QIAGEN) was added, and RNA further purified using the RNeasy mini kit (QIAGEN).

Analysis of the Production of Sialic Acid-Like Molecules by M. smithii

Reverse-phase HPLC analysis of cellular extracts—M. smithii was cultured in MBC medium, in a batch fermenter, to stationary phase (6 d incubation). Cells were collected by centrifugation, washed three times in PBS, snap frozen in liquid nitrogen, and stored at −80° C. Sialic acid content was assayed using established protocols (Manzi et al., (1995) Current Protocols in Molecular Biology)). Briefly, sialic acids were liberated by homogenization of the cell pellet (−30-50 mg wet weight) in 0.5 ml of 2M acetic acid with subsequent incubation of the homogenate for 3 h at 80° C. Samples were filtered through Microcon 10 filters (Millipore) and the filtrate, containing free sialic acid, was dried (speed-vacuum). The released sialic acid was derivatized with DMB (1,2-diamino-4,5-methylene-dioxybenzene) to yield a fluorescent adduct, which was analyzed by C18 reverse phase high-pressure liquid chromatography (RP-HPLC; Dionex DX-600 workstation). Sialic acid-like molecules were quantified by comparison to known amounts of derivatized standards [N-acetylneuraminic acid (Neu5Ac) and Nglycolylneuraminic acid (Neu5Gc)], and blanks (buffer alone).

Histochemical studies—M. smithii strains PS and F1 were grown in MBC as above. Bacteroides thetaiotaomicron VPI-5482, and Bifidobacterium longum NCC2705 were grown under anaerobic conditions in TYG medium to stationary phase and used as negative controls. Escherichia coli strain K92 (ATCC 35860), which is known to produce sialic acid (Egan et al., (1977) Biochemistry 16:3687-92), was incubated in 1419 medium (ATCC) to stationary phase and used as a positive control. All strains were fixed in 1.5 ml conical plastic tubes in either 4% paraformaldehyde or 100% ethanol for at least 8 h at 4° C. Samples were then washed with PBS and stored at −20° C. in 50% ethanol, 20 mM Tris and 0.1% IGEPAL CA-630 (Sigma; prepared in deionized water) until assayed. Samples were diluted in deionized water, placed on coated glass slides (Cel-Line/Erie Scientific Co.), air-dried, dehydrated in graded ethanols (50%, 80%, 100%), treated with blocking buffer (0.3% Triton X-100, 1% BSA in PBS; 30 min at room temperature), and then incubated with 10 μg/ml fluorescein-labeled Sambucus nigra lectin (SNA; Vector Laboratories; specificity, Neu5Acα2,6Gal/GalNAc epitopes) for 1 h at room temperature. Slides were subsequently washed with PBS, stained with 4′,6-diamidino-2-phenylindole (DAPI, 2 μg/ml; 5 min at room temperature), washed with de-ionized water, and mounted in PBS/glycerol. Slides were visualized with an Olympus BX41 microscope and photographed using a Q Imaging QICAM camera and OpenLab software (Improvision, Inc., v.3.1.5).

Transmission Electron Microscopy (TEM) of M. smithii.

Cells were harvested at day 6 of growth in the batch fermentor, and cellular morphology was defined by TEM using methods identical to those described previously for B. thetaiotaomicron (Sonnenburg et al., (2005) Science 307:1955-9). TEM studies of M. smithii present in the ceca of gnotobiotic mice that had been colonized for 14 d with the archaeon were conducted using the same protocol.

Microanalytic Biochemical Analyses of Cecal Samples Recovered from Gnotobiotic Mice

Extraction of metabolites from cecal contents—For measurement of ammonia and urea levels, perchloric acid extracts were prepared from 2 mg of freeze-dried cecal contents. [Contents were collected with a 10 μl inoculation loop, quick frozen in liquid nitrogen, and lyophilized at −35° C.] The lyophilized sample was homogenized in 0.2 ml of 0.3M perchloric acid at 1° C.

For the remaining metabolites, alkali and acid extracts were prepared from 4 mg of dried cecal samples that were homogenized in 0.4 ml 0.2M NaOH at 1° C. For the alkali extract, an 80 μl aliquot was removed, heated for 20 min at 80° C. and then neutralized with 80 μl of 0.25M HCl and 100 mM Tris base. For the acid extract, a 60 μl aliquot was removed and added to 20 μl 0.7M HCl, heated for 20 min at 80° C., and then neutralized with 40 μl 100 mM Tris base. Protein content was determined in the alkali extracts using the Bradford method (Bio Rad).

Metabolite assays—The sample concentrations for ammonium and urea were high enough so that direct fluorometric measurements could be used for detection. However, to measure the low sample concentrations for asparagine, glutamate, glutamine, α-ketoglutarate and ethanol, protocols were adapted from previously established pyridine nucleotide-linked assays, an “oil well” technique, and enzymatic cycling amplification (Passonneau et al., (1993) Enzymatic Analysis:A Practical Guide). All chemicals and enzymes were from Sigma unless otherwise noted.

Ammonium and Urea: For measurement of ammonium, a 20 μl aliquot of a perchloric acid extract of a given sample of cecal contents was added to 1 ml of a solution containing 50 mM imidazole HCl (pH 7.0), 0.2 mM α-ketoglutarate, 0.5 mM EDTA, 0.02% BSA, 10 μM NADH, and 10 μg/ml beef liver glutamate dehydrogenase (in glycerol; specific activity, 40 units/mg protein). Following a 40 min incubation at 24° C., fluorescence was measured using a Ratio-3 system filter fluorometer (Farrand Optical Components and Instruments, Valhalla, N.Y.; excitation at 360 nm; emission at 460 nm). Sample blanks were run that lacked added glutamate dehydrogenase. Ammonium acetate standards were carried throughout all steps.

To measure urea concentrations, 2 μl of a 50 mg/ml solution of Jack bean urease (50 units/mg) was added to the same sample used to determine ammonium levels. Following a 40 min incubation at 24° C., urea levels were defined based on a further reduction in fluorescence. Control sample blanks lacked added urease. Reference urea standards were carried throughout all steps.

Asparagine: A 0.5 μl aliquot of the alkali extract of a given sample of cecal contents was added to 0.5 μl of a solution containing 50 mM Trizma HCl (pH 8.7), 0.04% BSA, and 4 μg/ml E. coli asparaginase (160 units/mg protein). Sample blanks lacked added asparaginase. After a 30 min incubation at 24° C., 2 μl of a solution containing 50 mM Trizma HCl (pH 8.1), 10 μM α-ketoglutarate, 10 μM NADH, 4 mM freshly prepared ascorbic acid, 10 μg/ml of pig heart glutamic-oxalacetic transaminase (220 units/mg protein), plus 5 μg/ml beef heart malic dehydrogenase (2800 units/mg protein) was added, and the resulting mixture was incubated for 30 min at 24° C. One microliter of 0.25M HCl was then introduced. After a 10 min incubation at 24° C., a 2 μl aliquot of the reaction mixture was transferred to 0.1 ml of NAD cycling reagent for 20,000 cycles of amplification and the amplified product measured according to methods described by Passonneau and Lowry ((1993) Enzymatic Analysis:A Practical Guide). Sample blanks lacked added asparaginase. Reference asparagine standards were carried throughout all steps.

Glutamate and Glutamine: A 0.1 μl aliquot from an acid extract of a given sample of cecal contents was added to 0.1 μl of reagent containing 100 mM Na acetate (pH 4.9), 20 mM HCl, 0.4 mM EDTA and 50 μg/ml E. coli glutaminase (780 units/mg protein). Another 0.1 μl aliquot of the cecal contents was added to the same reagent in a parallel reaction that lacked added glutaminase (to measure glutamate alone). Following a 60 min incubation at 24° C., 2 μl of a solution containing 50 mM Tris acetate (pH 8.5), 0.1 mM NAD+, 0.1 mM ADP and 50 μg/ml beef liver glutamate dehydrogenase (120 units/mg protein; Roche) was added to both reaction mixtures, which were subsequently incubated for 30 min at 24° C. The reactions were terminated by addition of 1 μl of 0.2M NaOH and then heated for 20 min at 80° C. A 2 μl aliquot was subsequently transferred to 0.1 ml NAD cycling reagent and subjected to 20,000 cycles of amplification. Reference glutamine and glutamate standards were carried throughout all steps.

α-Ketoglutarate—A 0.5 μl aliquot from an given alkali extract was added to 0.5 μl of reagent containing 100 mM imidazole acetate (pH 6.5), 0.04% BSA, 50 mM ammonium acetate, 0.2 mM ADP, 4 mM ascorbic acid (freshly prepared), 40 μM NADH and 20 μg/ml beef liver glutamate dehydrogenase (120 units/mg protein; Roche). Following a 30 min incubation at 24° C., the reaction was terminated by adding 0.5 μl of 0.2M HCl. A 1 μl aliquot was transferred to 0.1 ml NAD cycling reagent and subjected to 30,000 cycles of amplification. α-Ketoglutarate standards were carried throughout all steps.

Ethanol: A 0.5 μl aliquot of an acid extract from cecal contents was added to 0.5 μl of a solution consisting of 5 mM Tris HCl (pH 8.1), 0.04% BSA, 0.1 mM NAD+, and 20 μg/ml yeast alcohol dehydrogenase (350 units/mg protein). Following a 60 min incubation at 24° C., 1 μl of 0.15M NaOH was added and the mixture heated for 20 min at 80° C. A 0.5 μl aliquot of this reaction mixture was transferred to 0.1 ml of NAD cycling reagent and amplified 5000-fold. Ethanol standards were carried throughout all steps.

Whole Genome Genotyping with Custom M. smithii GeneChips

GeneChips were manufactured by Affymetrix (http://www.affymetrix.com), based on the sequence of the PS strain genome (see Table 12 for details of the GeneChip design). Duplicate cultures of M. smithii strains PS (ATCC 35061), F1 (DSMZ 2374), ALI (DSMZ 2375) and B181 (DSMZ 11975), were grown in 125 ml serum bottles as described above. Genomic DNA was prepared from each strain using the QIAGEN Genomic DNA Isolation kit: mutanolysin (Sigma; 2.5 U/mg wet wt. cell pellet) was added to facilitate lysis of the microbes. DNA (5-7 μg) was further purified by phenolchloroform extraction and then sheared by sonication to <200 bp, labeled with biotin (Enzo BioArray Terminal Labeling Kit), denatured at 95° C. for 5 min, and hybridized to replicate GeneChips using standard Affymetrix protocols (http://www.affymetrix.com). M. smithii genes represented on the GeneChip were called “Present” or “Absent” by DNA-Chip Analyzer v1.3 (dChip; www.biostat.harvard.edu/complab/dchip/) using modeled (PM/MM ratio) data.

Statistical Analysis

Pairwise comparisons were made using unpaired Student's t-test. One-way ANOVA, followed by Tukey's post hoc multiple comparison test, was used to determine the statistical significance of differences observed between three groups.

Development of PHAT (Pressurized Heated Anaerobic Tank) System

A system for culturing M. smithii in 96-well plate format was designed and constructed in the following manner (See FIG. 15). Three stainless steel paint canisters (Binks, 83S-210, 2 gallon size) were modified for incubation of plates at 37° C. in an oxygen-free gas mix of 20% CO₂/80% H₂ at a pressure of 30 psi, where all of these growth parameters can be monitored and recorded.

The canisters are heated using Electro-Flex Heat brand Pail Heaters controlled by a custom designed controller consisting of a 16A2120 temperature/process control (Love Controls), an RTD (resistance temperature detector) probe to measure internal tank temperature, and several safety features to prevent overheating or burns.

The system is pressurized with oxygen-free gas that has flowed through a custom-built oxygen scrub. Commercially available gas mixes used for culturing M. smithii contain trace levels of oxygen that would kill the organism: thus, the gas mixture must be passed through an oxygen scrub. This scrub consists of a glass tube filled with copper mesh that is heated to 350° C. with heating tape (HTS/Amptek Duo-Tape), controlled by a benchtop power controller (HTS/Amptek BT-Z). The oxygen scrub is covered with insulating tape and secured behind a heat resistant polyetherimide case. Pressure in each tank is measured and recorded with a digital manometer (LEO record, Omni Instruments).

The system is housed inside an anaerobic chamber (COY laboratories) to allow inspection and manipulation of cultures and plates without exposing M. smithii to oxygen. Each tank can house 30 standard volume 96-well plates, which can be analyzed inside the COY anaerobic chamber with a microplate reader (BioRad) that monitors growth by measuring optical density.

Statin Susceptibility

Stock solutions (100×) of atorvastatin were prepared in methanol, pravastatin in ethanol, and rosuvastatin in DMSO (dimethyl sulfoxide) to concentrations of 100 mM, 10 mM and 1 mM. 1.5 μl of the stock solutions were added to wells in 96-well plates and transferred to the COY anaerobic chamber where they were kept for at least 24 hours to become anaerobic. 150 microliters of actively growing Methanobrevibacter smithii cultures were then added to each well (excluding medium+drug blanks) to bring the drug concentrations to 1 mM, 100 μM and 10 μM, respectively. The plates were incubated in the newly developed pressurized heated anaerobic tank system in a 4:1 mixture of oxygen-scrubbed H₂ and CO₂ at a pressure of 30 psi. Cultures grown in 1% ethanol, methanol and DMSO were used as controls. Growth was measured by determining optical density at 600 nm using the BioRad microplate reader (model 680).

Starting cultures of M. smithii strains [DSMZ 861 (PS), 2374 (F1), 2375 (ALI) and 11975 (B181)] were grown in 96 well plates in 150 μl volume/well of Methanobrevibacter complex medium (MBC) supplemented with 3 g/liter formate, 3 g/liter acetate, and 33 ml/liter of 2.5% Na₂S (added just before use). Each condition was tested in triplicate with the average measurement plotted.

Example 1 M. smithii Genome Description

The 1,853,160 base pair (bp) genome of the M. smithii type strain PS contains 1,795 predicted protein coding genes (Tables 1-4), 34 tRNAs, and two rRNA clusters. Some observations on the genome itself are as follows:

Elements that Affect Genome Evolution

The M. smithii PS genome contains multiple elements that can influence genome evolution, including 30 transposases, an integrated prophage (−38 kb; MSM1640-92), eight insertion sequence (IS) elements, 16 genes involved in DNA repair, 9 restriction-modification (R-M) system subunits, and four predicted integrases (Table 4).

Several lytic phages have been reported to infect M. smithii, including a 69 kb linear phage known as PG that belongs to the ψM1-like viruses (Prangishvili et al. (2006) Virus Res 117:52-67), and another 35 kb phage (PMS11; Calendar (2005) The Bacteriophages). The PG phage is AT-rich, heavily nicked, and lytic (burst size, 30-90), with a latent period of 3-4 h (Bertani et al. (1985) EMBO Workshop on Molecular Genetics of Archaebacteria and the International Workshop on Biology and Biochemistry of Archaebacteria, pg. 398). BLAST comparisons of the 52 predicted genes in the integrated prophage of M. smithii PS against known phage genes revealed only a few homologs (Table 13). One of the prophage genes (MSM1691) encodes a pseudomurein endoisopeptidase (PeiW): this enzyme may function to cleave M. smithii's cell wall and contribute to autolysis, as related enzymes in a defective Methanothermobacter wolfeii prophage have been shown to do (Luo et al., FEMS Microbiology Letters 208:47-51). The specific ends of the prophage genome could not be identified, and further studies are needed to determine whether the prophage is active and lytic.

The eight insertion sequence (IS) elements in M. smithii's genome (Table 4) range in length from 137 by (MSM1519) to 1013 by (MSM0527) and all are ISM1 (family ISNCY) according to ISfinder (Siguier et al., (2006) Nucleic Acids Res 34:D32-6; http://www-is.biotoul.fr/). ISM1 is a mobile IS element (Hamilton and Reeve (1985) Molecular Genetics and Genomics 200:47-59). IS elements promote genome evolution and plasticity through recombination, gene loss and, potentially, lateral gene transfer (Brugger et al., (2002) FEMS Microbiol Lett 206:131-41).

Transcriptional Regulation

M. smithii PS contains 60 predicted transcriptional regulators, including homologs of known nutrient sensors [e.g., a HypF family member (maturation of hydrogenases), a PhoU family member (phosphate metabolism), and a NikR family member (nickel)], plus five regulators of amino acid metabolism (Table 3). However, several GO categories related to environmental sensing and regulation (e.g., two-component systems; GO:0000160) are significantly depleted in its proteome compared to the proteomes of methanogens that live in terrestrial or aquatic environments (Table 6). In contrast, B. thetaiotaomicron, which uses complex, structurally diversified glycans as its principal nutrient source, possesses a large and diverse arsenal of nutrient sensors including 32 hybrid two-component systems plus 50 ECF-type sigma factors and 25 anti-sigma factors (Sonnenburg et al, (2006) PNAS 103:8834-9; Xu et al., (2003) Science 299:2074-6). This relative paucity of nutrient sensors may reflect the fact that M. smithii's niche is restricted, and its nutrient substrates are relatively small, readily diffusible molecules that may not require extensive machinery for their recognition.

Bile Acid Detoxification

In humans, cholic and chenodeoxycholic acids are synthesized in the liver and during their enterohepatic circulation undergo transformation by the intestinal microbiota to an array of metabolites (Hylemon and Harder (1998) FEMS Microbiol Rev 22:475-88). Bile acids and their metabolites have microbicidal activity and a genetically engineered deficiency of the bile acid-activated nuclear receptor FXR leads to reduced bile acid pools and bacterial overgrowth (Inagaki et al., (2006) PNAS 103:3920-5). Both M. smithii and M. stadtmanae encode a sodium:bile acid symporter (MSM1078), a conjugated bile acid hydrolase (CBAH; MSM0986), a short chain dehydrogenase with homology to a 7α-hydroxysteroid dehydrogenase (MSM0021). This is consistent with in vitro studies of M. smithii that demonstrate it is not inhibited by 0.1% deoxycholic acid (Miller et al, (1982) Appl Environ Microbiol 43:227-32).

We compared the proteome of M. smithii with the proteomes of (i) Methanosphaera stadtmanae, a methanogenic Euryarchaeote that is a minor and inconsistent member of the human gut microbiota (Eckburg et al., (2005) Science 308:1635-38), (ii) nine ‘non-gut methanogens’ recovered from microbial communities in the environment, and (iii) these non-gut methanogens plus an additional 17 sequenced Archaea (‘all archaea’) (Table 5).

Compared to non-gut methanogens and/or all archaea, M. smithii and M. stadtmanae are significantly enriched (binomial test, p<0.01) for genes assigned to GO (gene ontology) categories involved in surface variation (e.g., cell wall organization and biogenesis, see below), defense (e.g., multi-drug efflux/transport), and processing of bacteria-derived metabolites (Tables 6 and 7).

The M. smithii and M. stadtmanae genomes exhibit limited global synteny (FIG. 4) but share 968 proteins with mutual best BLAST hit e-values ≦10-20 (46% of all M. smithii proteins; Table 8). A predicted interaction network of M. smithii clusters of orthologous groups (COGs) based on STRING, a database of predicted functional associations between proteins (von Mering et al., (2003) Nucleic Acids Res 31:258-61), shows that it contains more COGs for persistence, improved metabolic versatility, and machinery for genomic evolution compared to M. stadtmanae (FIG. 5 and Table 9).

Cell Surface Variation

The ability to vary capsular polysaccharide surface structures in vivo by altering expression of glycosyltransferases (GTs) is a feature shared among sequenced bacterial species that are prominent in the distal human gut microbiota (Sonnenburg et al., (2005) Science 307:1955-59; Sonnenburg et al., (2006) PNAS 103:8834-39; Mazmanian et al., (2005) Cell 122:107-118; Coyne et al., (2005) Science 307:1778-81). Transmission EM studies of M. smithii harvested from gnotobiotic mice after a 14 day colonization revealed that it too has a prominent capsule (FIG. 1A). The proteomes of both human gut methanogens also contain an arsenal of GTs [26 in M. smithii and 31 in M. stadtmanae; see Table 10 for a complete list organized based on the Carbohydrate Active enZyme (CAZy) classification scheme (http://www.cazy.org; (Coutinho et al., (1999) Recent Advances in Carbohydrate Bioengineering)]. Unlike the sequenced Bacteroidetes, which possess large repertoires of glycoside hydrolases (GH) and carbohydrate esterases (CE) not represented in the human ‘glycobiome’, neither gut methanogen has any detectable GH or CE family members (FIG. 1B). Both M. smithii and M. stadtmanae dedicate a significantly larger proportion of their ‘glycobiome’ to GT2 family glycosyltransferases than any of the sequenced nongut associated methanogens (binomial test; p<0.00005; FIG. 1B). These GT2 family enzymes have diverse predicted activities, including synthesis of hyaluronan, a component of human glycosaminoglycans in the mucosal layer.

Sialic acids are a family of nine-carbon sugars that are abundantly represented in human mucus- and epithelial cell surface-associated glycans (Vimr et al., (2004) Microbiol Mol Biol Rev 68:132-53). N-acetylneuraminic acid (Neu5Ac) is the predominant type of sialic acid found in our species. Unique among sequenced archaea, M. smithii has a cluster of genes (MSM1535-1540) that encode all enzymes necessary for de novo synthesis of sialic acid from UDP-N-acetylglucosamine (i.e. UDP-GlcNAc epimerase, Neu5Ac synthase, CMP-Neu5Ac synthetase, and a putative polysialtransferase) (FIG. 1C). Biochemical analysis of extracts prepared from cultured M. smithii, plus histochemical staining of the microbe with the sialic-acid specific lectin, Sambucus nigra 1 agglutinin (SNA), confirmed the presence of a molecular species that co-elutes with a sialic acid standard in this analytic HPLC system (FIG. 6A-C). Taken together, our findings indicate that M. smithii has developed mechanisms to decorate its surface with carbohydrate moieties that mimic those encountered in the glycan landscape of its intestinal habitat.

The genomes of both human gut methanogens also encode a novel class of predicted surface proteins that have features similar to bacterial adhesins (48 members in M. smithii and 37 in M. stadtmanae). A phylogenetic analysis indicated that each methanogen has a specific clade of these Adhesin-Like Proteins (ALPs; FIG. 7). A subset of the M. smithii ALPs has homology to pectin esterases (GO:0030599): this GO family, which is significantly enriched in this compared to other Archaea based on the binomial test (p<0.0005; Table 6), is associated with binding of chondroitin, a major component of mucosal glycosaminoglycans. Several other M. smithii ALPs have domains predicted to bind other sugar moieties (e.g. galactose-containing-glycans; FIG. 7A). Both methanogens also have ALPs with peptidase-like domains (see Table 11 for a complete list of InterPro domains).

Example 2 Methanogenic and Non-Methanogenic Removal of Bacterial End-Products of Fermentation

Compared to other sequenced non-gut associated methanogens, M. smithii has significant enrichment of genes involved in utilization of CO₂, H₂ and formate for methanogenesis (GO:0015948; Table 6). They include genes that encode proteins involved in synthesis of vitamin cofactors used by enzymes in the methanogenesis pathway [methyl group carriers (F₄₃₀ and corrinoids); riboflavin (precursor for F₄₃₀ biosynthesis); and coenzyme M synthase (involved in the terminal step of methanogenesis)] (see Table 7 for a list of these genes, and FIG. 2A for the metabolic pathways). M. smithii also has an intact pathway for molybdopterin biosynthesis to allow for CO₂ utilization (FIG. 8). M. smithii also upregulates a formate utilization gene cluster (FdhCAB; MSM1403-5) for methanogenic consumption of this B. thetaiotaomicron-produced metabolite (Samuel and Gordon (2006) PNAS 103:10011-10016).

Our previous qRT-PCR and mass spectrometry studies revealed that co-colonization increased B. thetaiotaomicron acetate production [acetate kinase (BT3963) 9-fold upregulated vs. B. thetaiotaomicron-mono-associated controls; P<0.0005; n=4-5 animals/group (Samuel and Gordon (2006) PNAS 103:10011-10016)]. Although acetate is not converted to methane by M. smithii (Miller et al., (1982) Appl. Environ. Microbiol. 43:227-32), we found that its proteome contains an ‘incomplete reductive TCA cycle’ that would allow it to assimilate acetate [Acs (acetyl-CoA synthase, MSM0330), Por (pyruvate:ferredoxin oxidoreductase, MSM0560), Pyc (pyruvate carboxylase, MSM0765), Mdh (malate dehydrogenase, MSM1040), Fum (fumarate hydratase, MSM0477, MSM0563, MSM0769, MSM0929), Sdh (succinate dehydrogenase, MSM1258), Suc (succinyl-CoA synthetase, MSM0228, MSM0924), and Kor (2-oxoglutarate synthase, MSM0925-8) in FIG. 2A]. Two important M. smithii genes associated with this pathway participate in acetate assimilation: Por (pyruvate:ferredoxin oxidoreductase) as well as Cab (carbonic anhydrase, MSM0654), which converts CO₂ to bicarbonate, the substrate for Por.

M. smithii also possesses enzymes that in other methanogens facilitate utilization of two other products of bacterial fermentation, methanol and ethanol (Fricke et al, J Bacteriol 188:642-58; Berk et al., (1997) Arch Microbiol 168:396-402). M. smithii's genome contains a methanol:cobalamin methyltransferase (MtaB, MSM0515), an NADP-dependent alcohol dehydrogenase (Adh, MSM1381), and an F₄₂₀-dependent NADP reductase (Fno, MSM0049) [see FIG. 2A for pathway information]. Biochemical studies confirmed a significant decrease in ethanol levels in the ceca of co-colonized mice [11±2.5 μmol/g total protein in cecal contents versus 35±10 μmol/g and 15 μmol/g in B. thetaiotaomicron and M. smithii mono-associated animals respectively; p<0.05; FIG. 2B]. Expression of B. thetaiotaomicron's alcohol dehydrogenases (BT4512 and BT0535) is not altered by co-colonization (Samuel and Gordon (2006) PNAS 103:10011-10016), indicating that the reduction in cecal ethanol levels observed in co-colonized mice is not due to diminished bacterial production but rather to increased archaeal consumption.

Collectively, these findings indicate that M. smithii supports methanogenic and non-methanogenic removal of diverse bacterial end-products of fermentation: this capacity may endow it with a great flexibility to form syntrophic relationships with a broad range of bacterial members of the distal human gut microbiota.

Example 3 M. smithii Utilization of Ammonia as a Primary Nitrogen Source

Subject metabolism of amino acids by glutaminases associated with the intestinal mucosa (Wallace (1996) J Nutr 126:1326 S), or deamination of amino acids during bacterial degradation of dietary proteins yields ammonia (Cabello et al., (2004) Microbiology 150:3527-46). The M. smithii proteome contains a transporter for ammonium (AmtB; MSM0234) plus two routes for its assimilation: (i) the ATP—utilizing glutamine synthetase—glutamate synthase pathway which has a high affinity for ammonium and thus is advantageous under nitrogen-limited conditions; and (ii) the ATP-independent glutamate dehydrogenase pathway which has a lower affinity for ammonium (Dumitru et al., (2003) Appl. Environ. Microbiol. 69:7236-41).

Microanalytic biochemical assays revealed a ratio of glutamine to 2-oxoglutarate concentration that was 15-fold lower in the ceca of co-colonized gnotobiotic mice compared to animals colonized with M. smithii alone, and 2-fold lower compared to B. thetaiotaomicron mono-associated subjects (p<0.0001; FIG. 2C). In addition, levels of several polar amino acids were also significantly reduced in mice with the saccharolytic bacterium and methanogen (FIG. 2D), providing additional evidence for a nitrogen-limited gut environment. The key M. smithii genes involved in ammonia assimilation, particularly those in the high affinity glutamine synthetase-glutamate synthase pathway are GlnA (glutamine synthetase, MSM1418) and GltA/GltB (two subunits of glutamate synthase, MSM0027, MSM0368); FIG. 2A. GeneChip analysis of the transcriptional responses of B. thetaiotaomicron to co-colonization with M. smithii indicated that it also upregulates a high affinity glutamine synthase [BT4339; 2.4-fold vs. B. thetaiotaomicron monoassociated mice; n=4-5 mice/group; p<0.001; (Samuel et al., (2006) PNAS 103:10011-10016)]. This prioritization of ammonium assimilation by B. thetaiotaomicron and M. smithii is accompanied by a modest but not statistically significant decrease in cecal ammonium levels in co-colonized subjects (13.4±1.8 μmol/g dry weight of cecal contents vs. 142.45±1.0 in M. smithii- and 14.4±0.9 in B. thetaiotaomicron-monoassociated animals; n=5-15/group; FIG. 2E). Together, these studies indicate that ammonium represents a source of nitrogen for M. smithii when it exists in isolation in the gut of gnotobiotic mice, and that it may compete with B. thetaiotaomicron for this nutrient resource.

Example 4 Considering Targets for Development of Anti-M. smithii Agents

Manipulation of the representation of M. smithii in our gut microbiota could provide a novel means for treating obesity. Functional genomics studies in gnotobiotic mice illustrate one way to approach the issue. For example, inhibitors exist for several M. smithii enzymes. A class of N-substituted derivatives of para-aminobenzoic acid (pABA) interfere with methanogenesis by competitively inhibiting ribofuranosylaminobenzene 5′-phosphate synthase [RfaS; MSM0848; (Dumitru et al., (2003) Appl. Environ. Microbiol. 69:7236-41)].

Archaeal membrane lipids, unlike bacterial lipids, contain ether-linkages. A key enzyme in the biosynthesis of archaeal lipids is hydroxymethylglutaryl (HMG)-CoA reductase (MSM0227), which catalyzes the formation of mevalonate, a precursor for membrane (isoprenoid) biosynthesis (23). HMG-CoA reductase inhibitors (statins) inhibit growth of Methanobrevibacter species in vitro (23).

We designed a custom GeneChip containing probesets directed against 99.1% of M. smithii's 1795 known and predicted protein-coding genes (see Table 12 for details). This GeneChip was used to perform whole genome genotyping of M. smithii PS (control) plus three other strains recovered from the feces of healthy humans: F1 (DSMZ 2374), ALI (DSMZ 2375) and B181 (DSMZ 11975). Replicate hybridizations indicated that 100% of the open reading frames (ORFs) represented on the GeneChip were detected in M. smithii PS, while 90-94% were detected in the other strains, including the potential drug targets mentioned above (Table 2 and FIG. 3). Approximately 50% of the undetectable ORFs in each strain encode hypothetical proteins. The other undetectable genes are involved in genome evolution [e.g., recombinases, transposases, IS elements, and type II restriction modification (R-M) systems], or are components of a putative archaeal prophage in strain PS, or are related to surface variation, including several ALPs (e.g., MSM0057 and MSM1585-90; FIG. 7). Strains F1 and ALI also appear to lack redundant gene clusters encoding subunits of formate dehydrogenase (MSM1462-3) and methyl-CoM reductase (MSM0902-3) that are found in the PS strain (the latter cluster is also undetectable in strain B181). In addition, the only methanol utilization cluster present in the PS strain (MSM1515-8) was not detectable in strain F1 (Table 2).

To further assess the degree of nucleotide sequence divergence among M. smithii strains, we compared the sequenced PS type strain to a 78 Mb metagenomic dataset generated from the aggregate fecal microbial community genome (microbiome) of two healthy humans (Gill et al., (2006) Science 312:1355-59). Their sequenced microbiomes contained 92% of the ORFs in the type strain (Table 2), including the potential drug targets described above. Several R-M system gene clusters (MSM0157-8, MSM1743, MSM1746-7), a number of transposases, a DNA repair gene cluster (MSM0689-95), and all ORFs in the prophage were not evident in the two microbiomes. Sequence divergence was also observed in 33 of the 48 ALP genes plus two ‘surface variation’ gene clusters (MSM1289-1398 and MSM1590-1616) that encode 11 glycosyltransferases and 9 proteins involved in pseudomurein cell wall biosynthesis (FIG. 9). A redundant methyl-CoM reductase cluster (MSM0902-3), an F₄₂₀-dependent NADP oxidoreductase (MSM0049) involved in consumption of bacteria-derived ethanol, and two subunits of the bicarbonate ABC transporter (MSM0990-1; carbon utilization) exhibited heterogeneity in the M. smithii populations present in the gut microbiota of these two adults (Table 2 and FIG. 9).

In yet another type of analysis, we compared the sequenced genome of M. smithii strain PS to the sequenced genomes of 11 other strains, isolated from the fecal microbiota of a pair of adult female monozygotic twins and two other unrelated individuals. The results, summarized in Table A, reveal a set of 1436 genes that are represented in all of these human isolates as well as the PS type strain. These genes, which include the gene encoding HMG-CoA reductase, comprise a human gut-associated M. smithii “core” genome.

Example 5 Effect of HMG-CoA Reductase Inhibitors Administration

The PHAT system was used to culture 4 strains of M. smithii (DSMZ 861 (PS), 2374 (F1), 2375 (ALI) and 11975 (B181)) in 96-well plate format, and to test their sensitivities to various HMG-CoA reductase inhibitors. Preliminary results indicate that atorvastatin (Lipitor®), pravastatin (Pravachol®) and rosuvastatin (Crestor®) inhibit all strains tested at concentrations of 1 millimolar. Atorvastatin and rosuvastatin also inhibit all strains at 100 micromolar concentrations (FIG. 10-13; Tables 14-17). None of these three statins had any affect on the growth of a dominant human gut-associated saccharolytic bacterium, Bacteroides thetaiotaomicron (FIG. 14).

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MSM1697* MSM1698* MSM1699* MSM1700* MSM1701* MSM1702 MSM1703 MSM1704* MSM1705 MSM1706 MSM1707 MSM1708* MSM1709 MSM1710 MSM1711* MSM1712* MSM1713 MSM1714 MSM1715 MSM1716 MSM1717 MSM1718* MSM1719 MSM1720* MSM1721* MSM1722 MSM1723 MSM1724 MSM1725 MSM1726* MSM1727* MSM1728 MSM1729* MSM1730 MSM1731 MSM1732* MSM1733 MSM1734* MSM1735 MSM1736 MSM1737* MSM1738* MSM1739* MSM1740* MSM1741* MSM1742* MSM1743* MSM1744* MSM1745* MSM1746* MSM1747* MSM1748* MSM1749* MSM1750* MSM1751* MSM1752* MSM1753* MSM1754* MSM1755* MSM1756* MSM1757* MSM1758* MSM1759* MSM1760* MSM1761* MSM1762* MSM1763* MSM1764* MSM1765* MSM1766* MSM1767* MSM1768* MSM1769 MSM1770 MSM1771 MSM1772 MSM1773 MSM1774 MSM1775 MSM1776 MSM1777 MSM1778 MSM1779 MSM1780 MSM1781 MSM1782 MSM1783 MSM1784 MSM1785 MSM1786 MSM1787 MSM1788 MSM1789 MSM1790 MSM1791 MSM1792 MSM1793 MSM1794 MSM1795 Families Individuals Strains Genes 4 5 11 1436 *Genes found in all strains examined. 11 strains, all isolated from human feces, were sequenced and their gene content compared to Methanobrevibacter smithii PS, the type strain. A total of 1436 genes were found in all strains examined to date.

TABLE 1 General features of the M. smithii PS genome compared to other sequenced Methanobacteriales Methano- Methano- Methano- thermobacter brevibacter sphaera thermoauto- smithii stadtmanae trophicus Genome Size (bp) 1,853,160 1,767,403 1,751,377 G + C content (%) 31 28 50 Coding Regions (%) 90 84 90 Number of ORFs 1795 1534 1869 rRNA operons 2 4 2 tRNA genes 34 40 39 tRNA genes with intron 1 1 3 Transposases (remnants) 2 (20) 1 (2) 0 Insertion Sequences 8 4 0 Restriction Modification 2/6/1 3/2/1 3/0/0 System Subunits (Type I/II/III) Putative Prophage Yes No No

TABLE 2 Predicted proteome of M. smithii strain PS and conservation among other strains and in the fecal microbiome of two healthy adults. M. smithil strain genotyping Human Gut Gene Annotation PS F1 ALI B181 Microbiome MSM0001 exoribonuclease VII, large subunit, XseA

MSM0002 integrase-recombinase protein

MSM0003 conserved hypothetical membrane protein (putative heme utilization/adhesion related)

MSM0004 predicted lysine decarboxylase

MSM0005 conserved hypothetical protein

MSM0006 conserved hypothetical protein

MSM0007 SAM-dependent methyltransferase ND

MSM0008 putative transposase

MSM0009 conserved hypothetical protein

MSM0010 N-acetyltransferase, GNAT family

MSM0011 hypothetical protein

MSM0012 conserved hypothetical protein

MSM0013 hypothetical protein

MSM0014 putative heat shock related protein

MSM0015 hypothetical protein

MSM0016 hypothetical protein

MSM0017 hypothetical protein

MSM0018 hypothetical protein

MSM0019 hypothetical protein

MSM0020 predicted O-linked GlnNAc transferase

MSM0021 short chain dehydrogenase (7-alpha-hydroxysteroid dehydrogenase)

MSM0022 hypothetical protein

MSM0023 uncharacterized protein predicted to be involved in DNA repair

MSM0024 hypothetical protein

MSM0025 long-chain-fatty-acid-CoA ligase

MSM0026 predicted transcriptional regulator

MSM0027 glutamate synthase, domain 2 with rubredoxin

MSM0028 SAM-dependent methyltransferase

MSM0029 putative calcium-binding protein

MSM0030 conserved hypothetical membrane protein

MSM0031 adhesin-like protein

MSM0032 hypothetical protein

MSM0033 ketopantoate reductase, ApbA

MSM0034 conserved hypothetical protein

MSM0035 hypothetical protein

MSM0036 hypothetical protein

MSM0037 hypothetical protein

MSM0038 hypothetical protein

MSM0039 hypothetical protein

MSM0040 conserved hypothetical protein

MSM0041 hypothetical protein

MSM0042 hypothetical protein

MSM0043 peptide methionine sulfoxide reductase, PMSR

MSM0044 PLP dependent aminotransferase (aspartate)

MSM0045 nucleotide-binding protein (putative ATPase involved in chromosome partitioning)

MSM0046 NADH oxidase

MSM0047 Chloramphenicol O-acetyltransferase

MSM0048 conserved hypothetical protein

MSM0049 F420-dependent NADP oxidoreductase, fno

MSM0050 predicted metal-binding protein

MSM0051 adhesin-like protein

MSM0052 adhesin-like protein

MSM0053 tRNA nucleotidyltransferase (CCA-adding enzyme)

MSM0054 2′-5′RNA ligase, LigT

MSM0055 predicted alternative 3-dehydroquinate synthase

MSM0056 archaeal fructose-1,6-biphosphate aldolase

MSM0057 adhesin-like protein

MSM0058 DNA helicase II

MSM0059 SAM-dependent methyltransferase

MSM0060 predicted archaeal kinase (GHMP kinase family)

MSM0061 predicted ATPase (AAA+ superfamily)

MSM0062 flavodoxin

MSM0063 amidohydrolase (PHP family)

MSM0064 conserved hypothetical protein

MSM0065 riboflavin-specific deaminase

MSM0066 N-acetylglucosamine-1-phosphate transferase, GT4 family

MSM0067 conserved hypothetical protein

MSM0068 hypothetical protein

MSM0069 conserved hypothetical protein

MSM0070 conserved hypothetical protein

MSM0071 methionyl-tRNA synthetase, MetG

MSM0072 putative exonuclease SBCC

MSM0073 DNA primase, large subunit (eukaryotic-type)

MSM0074 hypothetical protein

MSM0075 DNA primase, small subunit

MSM0076 conserved hypothetical protein

MSM0077 thymidylate kinase

MSM0078 dolichol kinase (cytidylyltransferase family)

MSM0079 CofH protein (7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO)/F420 biosynthesis

MSM0080 sulfopyruvate decarboxylase, comD

MSM0081 sulfopyruvate decarboxylase, comE

MSM0082 heterodisulfide reductase, subunit A, HdrA

MSM0083 heterodisulfide reductase, subunit B, HdrB

MSM0084 heterodisulfide reductase, subunit C, HdrC

MSM0085 putative ferredoxin

MSM0086 (2R)-phospho-3-sulfolactate synthase, ComA

MSM0087 putative transposase ND

MSM0088 conserved hypothetical protein

MSM0089 pyrroline-5-carboxylate reductase (NADP oxidoreductase, coenzyme F420-dependent), ProC

MSM0090 conserved hypothetical protein (UPF0058)

MSM0091 2,3-diphosphoglycerate synthase (putative GTPase)

MSM0092 putative adhesin-like protein

MSM0093 conserved hypothetical membrane-spanning protein (phage infection)

MSM0094 predicted transcription regulator (TetR family)

MSM0095 predicted phosphotransacetylase

MSM0096 undecaprenyl pyrophosphate synthase, UppS

MSM0097 Mg-dependent DNase, TatD

MSM0098 hypothetical protein

MSM0099 conserved hypothetical membrane protein

MSM0100 conserved hypothetical protein

MSM0101 precorrin-3 methylase, CbiF

MSM0102 cobalamin-independent methionine synthase, MetE

MSM0103 conserved hypothetical protein

MSM0104 conserved hypothetical protein

MSM0105 conserved hypothetical protein

MSM0106 conserved hypothetical protein

MSM0107 hydrogenase expression/formation protein, HypB

MSM0108 hydrogenase nickel incorporation protein, HypA

MSM0109 conserved hypothetical membrane-spanning protein

MSM0110 predicted transposase

MSM0111 hypothetical protein

MSM0112 ATP-dependent RNA helicase, elF-4A family

MSM0113 DNA helicase

MSM0114 hypothetical protein

MSM0115 conserved hypothetical protein

MSM0116 MobA-related protein

MSM0117 conserved hypothetical membrane protein

MSM0118 cell wall biosynthesis protein, MurD-like peptide ligase family

MSM0119 predicted nuclease

MSM0120 purine NTPase involved in DNA repair, Rad50

MSM0121 DNA repair exonuclease (SbcD/Mre11-family), Rad32

MSM0122 predicted ATPase

MSM0123 uncharacterized protein conserved in archaea

MSM0124 predicted phosphate-binding protein (PcrB family)

MSM0125 ribosomal protein L40e

MSM0126 conserved hypothetical protein

MSM0127 hypothetical protein

MSM0128 conserved hypothetical protein

MSM0129 nicotinamide mononucleotide adenylyltransferase, NadR

MSM0130 molybdenum cofactor biosynthesis protein, MoaE

MSM0131 molybdenum-binding protein, Mopl

MSM0132 conserved hypothetical protein

MSM0133 predicted thioesterase, FcbC

MSM0134 M42 glutamyl aminopeptidase/endo-glucanase

MSM0135 coenzyme F420-reducing hydrogenase, beta subunit

MSM0136 putative ferredoxin

MSM0137 putative archaeal flagellar protein D/E

MSM0138 predicted exonuclease

MSM0139 hypothetical protein

MSM0140 conserved hypothetical protein

MSM0141 dephospho-CoA kinase, CoaE

MSM0142 predicted ATPase (PP-loop superfamily)

MSM0143 conserved hypothetical membrane protein

MSM0144 hypothetical protein (putative ADP-ribosylation domain)

MSM0145 conserved hypothetical protein

MSM0146 type IV leader peptidase

MSM0147 CTP synthase (UTP-ammonia lyase), PyrG

MSM0148 predicted oxidoreductase, aldo/keto reductase family

MSM0149 predicted acetylesterase

MSM0150 hypothetical protein

MSM0151 hypothetical protein

MSM0152 Na+-driven multidrug efflux pump (MATE family), NorM

MSM0153 predicted phosphoglycerate mutase

MSM0154 homoserine dehydrogenase, ThrA

MSM0155 predicted allosteric regulator of homoserine dehydrogenase

MSM0156 Asp-tRNA(Asn)/Glu-tRNA(Gln) amidotransferase, C subunit

MSM0157 predicted type I restriction-modification enzyme, subunit S

MSM0158 type I restriction-modification system methylase, subunit S

MSM0159 adhesin-like protein

MSM0160 asparagine synthetase, AsnB

MSM0161 hypothetical protein

MSM0162 hypothetical protein

MSM0163 conserved hypothetical protein predicted to be involved in DNA repair

MSM0164 conserved hypothetical protein predicted to be involved in DNA repair

MSM0165 predicted exonuclease

MSM0166 predicted helicase

MSM0167 conserved hypothetical protein predicted to be involved in DNA repair (RAMP superfamily)

MSM0168 conserved hypothetical protein predicted to be involved in DNA repair

MSM0169 predicted CRISPR-associated protein

MSM0170 conserved hypothetical protein predicted to be involved in DNA repair (RAMP superfamily)

MSM0171 conserved hypothetical membrane protein (invasin/intimin cell- adhesion domain)

MSM0172 hypothetical protein

MSM0173 adhesin-like protein

MSM0174 O-acetylhomoserine sulfhydrylase (PLP-dependent), MET17

MSM0175 homoserine O-acetyltransferase, MetX

MSM0176 ribonuclease III (dsRNA-specific), Rnc

MSM0177 hypothetical protein

MSM0178 conserved hypothetical protein

MSM0179 hypothetical protein

MSM0180 hypothetical protein

MSM0181 ribosomal protein L37e

MSM0182 snRNP Sm-like protein

MSM0183 RNA-binding protein, PUA domain family

MSM0184 creatinine amidohydrolase

MSM0185 conserved hypothetical membrane protein

MSM0186 conserved hypothetical protein

MSM0187 rubredoxin

MSM0188 rubredoxin

MSM0189 acetyl/acyl transferase related protein

MSM0190 predicted ATPase

MSM0191 conserved hypothetical protein

MSM0192 argininosuccinate lyase, ArgH

MSM0193 ribosomal protein S27ae

MSM0194 ribosomal protein S24ae

MSM0195 uncharacterized protein conserved in archaea

MSM0196 archaeal DNA-dependent RNA polymerase, subunit E, RpoE

MSM0197 archaeal DNA-dependent RNA polymerase, subunit E, RpoE

MSM0198 inorganic pyrophosphatase

MSM0199 conserved hypothetical protein (PilT N-term./Vapc superfamily)

MSM0200 translation initiation factor alF-2, gamma subunit

MSM0201 ribosomal protein S6e

MSM0202 translation initiation factor alF-2, InfB

MSM0203 nucleoside diphosphate kinase, Ndk

MSM0204 ribosomal protein L24e

MSM0205 ribosomal protein S28e

MSM0206 ribosomal protein L7ae

MSM0207 predicted DNA-binding protein

MSM0208 predicted DNA-binding protein

MSM0209 ferredoxin

MSM0210 hypothetical protein

MSM0211 hypothetical protein

MSM0212 conserved hypothetical protein

MSM0213 archaeal histone, HMtA

MSM0214 threonine synthase (pyridoxal-phosphate dependent), ThrC

MSM0215 conserved hypothetical integral membrane protein

MSM0216 tryptophanyl-tRNA synthetase, TrpS

MSM0217 tRNA intron endonuclease, EndA

MSM0218 iron dependent transcriptional regulator (Fe2+-binding)

MSM0219 putative cysteine protease (transglutaminase-like superfamily)

MSM0220 chaperonin (TCP-1/cpn60 family), alpha subunit

MSM0221 adhesin-like protein

MSM0222 flavoprotein (Metallo-beta-lactamase superfamily), FpaA

MSM0223 conserved hypothetical protein

MSM0224 conserved hypothetical protein

MSM0225 conserved hypothetical protein

MSM0226 hypothetical protein

MSM0227 hydroxymethylglutaryl-CoA (HMG-CoA) reductase, HmgA

MSM0228 succinyl-CoA synthetase, alpha subunit, SucD

MSM0229 conserved hypothetical protein

MSM0230 putative transposase ND

MSM0231 3-dehydroquinate dehydratase

MSM0232 signal peptidase I

MSM0233 nitrogen regulatory protein P-II, GlnK

MSM0234 ammonium transporter

MSM0235 hypothetical protein

MSM0236 phosphohydrolase (HD superfamily)

MSM0237 3-polyprenyl-4-hydroxybenzoate decarboxylase, UbiX

MSM0238 precorrin-6B methylase, CbiT

MSM0239 conserved hypothetical protein

MSM0240 molybdopterin-guanine dinucleotide biosynthesis protein A, MobA

MSM0241 ribonuclease PH-related protein

MSM0242 ribonuclease PH, Rph

MSM0243 RNA-binding protein Rrp4

MSM0244 predicted exosome subunit

MSM0245 proteasome, alpha subunit, PsmA

MSM0246 ribonuclease P, subunit Rpp14

MSM0247 ribonuclease P, subunit p30

MSM0248 hypothetical protein

MSM0249 conserved hypothetical protein

MSM0250 conserved hypothetical membrane protein (putative zinc-finger domain, Znf265)

MSM0251 hypothetical protein

MSM0252 Na+-driven multidrug efflux pump, NorM

MSM0253 conserved hypothetical protein

MSM0254 hypothetical protein

MSM0255 putative transcription regulator (winged helix DNA-binding domain)

MSM0256 putative transposase

MSM0257 conserved hypothetical membrane protein

MSM0258 hypothetical protein (putative zinc-finger domain, Znf265)

MSM0259 hypothetical protein (putative zinc beta-ribbon superfamily)

MSM0260 archaea-specific RecJ-like exonuclease

MSM0261 conserved hypothetical protein

MSM0262 desulfoferrodoxin (dfx)

MSM0263 nitrogen fixation protein, NifU

MSM0264 cysteine desulfurase, NifS

MSM0265 O-acetylhomoserine sulfhydrylase

MSM0266 adhesin-like protein

MSM0267 NAD(P)H-dependent FMN reductase (multimeric flavodoxin)

MSM0268 cysteinyl-tRNA synthetase, CysS

MSM0269 predicted transcriptional regulator (lambda repressor-like)

MSM0270 serine acetyltransferase, CysE

MSM0271 cysteine synthase, CysK

MSM0272 endonuclease III

MSM0273 EPSP synthase (3-phosphoshikimate 1-carboxyvinyltransferase)

MSM0274 SAM-dependent methyltransferase (cyclopropane fatty acid synthase-related)

MSM0275 valyl-tRNA synthetase, ValS

MSM0276 conserved hypothetical protein

MSM0277 phenylalanyl-tRNA synthetase, beta subunit, PheT

MSM0278 hypothetical protein

MSM0279 conserved hypothetical protein (UPF0047 family)

MSM0280 predicted archaeal ATPase (AAA+ superfamily)

MSM0281 putative adhesin-like protein

MSM0282 adhesin-like protein

MSM0283 hypothetical protein

MSM0284 ribose 5-phosphate isomerase, RpiA

MSM0285 conserved hypothetical protein (UPF0179 family)

MSM0286 glycerol 1-phosphate dehydrogenase (Dehydroquinate synthase-like family)

MSM0287 prolyl-tRNA synthetase, ProS

MSM0288 conserved hypothetical protein (DUF121 daomain)

MSM0289 phosphomethylpyrimidine kinase (HMPP-kinase), ThiD

MSM0290 nitrate/sulfonate/bicarbonate ABC transporter, ATPase component, TauB

MSM0291 nitrate/sulfonate/bicarbonate ABC transporter, permease component, TauC

MSM0292 predicted metal-dependent membrane protease

MSM0293 cation transport ATPase, HAD family

MSM0294 conserved hypothetical protein

MSM0295 formate dehydrogenase accessory protein, FdhD

MSM0296 putative carboxymuconolactone decarboxylase

MSM0297 predicted exosome subunit

MSM0298 ribosomal protein L15e

MSM0299 conserved hypothetical protein

MSM0300 peptide/nickel ABC transporter, solute-binding component

MSM0301 peptide/nickel ABC transporter, permease component, DppB

MSM0302 peptide/nickel ABC transporter, permease component, DppC

MSM0303 peptide/nickel ABC transporter, ATP-binding component, DppD

MSM0304 peptide/nickel ABC transporter, ATP-binding component, DppF

MSM0305 conserved hypothetical membrane protein (IMP dehydrogenase related)

MSM0306 polyferredoxin, iron-sulfur binding

MSM0307 sugar kinase (ribokinase/pfkB superfamily)

MSM0308 formylmethanofuran:tetrahydromethanopterin formyltransferase, FtrC

MSM0309 conserved hypothetical membrane protein

MSM0310 polyferredoxin, iron-sulfur binding

MSM0311 polyferredoxin, iron-sulfur binding

MSM0312 [NiFe]-hydrogenase-3-type complex, large subunit/NADH:quinine oxidoreductase (complex I), subunit 49 K/NdhH/NuoD

MSM0313 [NiFe]-hydrogenase-3-type complex, small subunit/NADH:quinine oxidoreductase (complex I), subunit PSST/NdhK/NuoB

MSM0314 conserved hypothetical protein

MSM0315 predicted [NiFe]-hydrogenase-3-type complex Eha, membrane protein EhaL

MSM0316 hypothetical protein

MSM0317 NADH dehydrogenase (ubiquinone), subunit 1

MSM0318 conserved hypothetical membrane protein

MSM0319 NADH dehydrogenase I, subunit N related

MSM0320 predicted [NiFe]-hydrogenase-3-type complex Eha, membrane protein EhaG

MSM0321 conserved hypothetical membrane protein

MSM0322 predicted [NiFe]-hydrogenase-3-type complex Eha, membrane protein EhaE

MSM0323 conserved hypothetical membrane protein

MSM0324 conserved hypothetical membrane protein

MSM0325 conserved hypothetical membrane protein

MSM0326 conserved hypothetical membrane protein

MSM0327 UDP-glucose 4-epimerase (NAD dependent)

MSM0328 conserved hypothetical protein

MSM0329 DNA binding protein (regulator), xenobiotic response element family

MSM0330 acetyl-CoA synthetase, AMP-forming-related, Acs

MSM0331 2-oxoisovalerate ferredoxin oxidoreductase, delta subunit

MSM0332 2-oxoisovalerate ferredoxin oxidoreductase, alpha subunit

MSM0333 2-oxoisovalerate ferredoxin oxidoreductase, beta subunit

MSM0334 L-asparaginase, GatD,

MSM0335 archaeal glutamyl-tRNA(Gln) amidotransferase, subunit E, GatE

MSM0336 hypothetical protein

MSM0337 putative adhesin-like protein

MSM0338 hypothetical protein

MSM0339 hypothetical protein

MSM0340 thioredoxin reductase (NADPH), TrxB

MSM0341 hypothetical protein

MSM0342 putative transposase ND MSM0343 GMP synthase (glutamine-hydrolysing), subunit A, GuaA

MSM0344 hypothetical protein

MSM0345 GMP synthase (glutamine-hydrolysing), PP-ATPase domain/subunit, GuaA

MSM0346 conserved hypothetical protein

MSM0347 putative pyridoxal phosphate-dependent enzyme

MSM0348 conserved hypothetical protein

MSM0349 hypothetical protein

MSM0350 2-isopropylmalate synthase, LeuA

MSM0351 conserved hypothetical protein

MSM0352 predicted DNA modification methylase

MSM0353 conserved hypothetical protein

MSM0354 ATP-dependent 26S proteasome regulatory subunit, RPT1

MSM0355 predicted transcription factor (eukaryotic MBF1 related)

MSM0356 conserved hypothetical protein

MSM0357 conserved hypothetical membrane protein (possible Zinc-binding)

MSM0358 conserved hypothetical membrane protein

MSM0359 cell wall biosynthesis protein, MurD-like peptide ligase family

MSM0360 cell wall biosynthesis protein, phospho-N-acetylmuramoyl- pentapeptidetransferase family

MSM0361 carbamoyl-phosphate synthase, large subunit, CarB

MSM0362 coenzyme F420-reducing hydrogenase (Ni, Fe-hydrogenase maturation protease), delta subunit

MSM0363 predicted RNA methylase

MSM0364 transcriptional regulator (nickel-responsive), NikR

MSM0365 conserved hypothetical protein

MSM0366 hypothetical protein

MSM0367 conserved hypothetical protein

MSM0368 glutamate synthase (NADPH), subunit 2

MSM0369 glutamate synthase, subunit 3

MSM0370 glutamate synthase, subunit 1

MSM0371 predicted glutamine amidotransferase involved in pyridoxine biosynthesis, Pdx2

MSM0372 phycobiliprotein (PBS) lyase (HEAT repeat)

MSM0373 isocitrate/isopropylmalate dehydrogenase, LeuB

MSM0374 long-chain fatty-acid-CoA ligase (AMP-forming), CaiC

MSM0375 acetylglutamate kinase, ArgB

MSM0376 alcohol dehydrogenase (zinc-binding), GroES-like

MSM0377 4-diphosphocytidyl-2-methyl-D-erithritol synthase, IspD

MSM0378 SAM-dependent methyltransferase

MSM0379 glutamate N-acetyltransferase, ArgJ

MSM0380 hypothetical protein

MSM0381 conserved hypothetical protein

MSM0382 conserved hypothetical protein (PIN domain-like)

MSM0383 predicted phosphohydrolase, calcineurin-like superfamily

MSM0384 transcription factor, NACalpha-BTF3 related

MSM0385 anaerobic magnesium-protoporphyrin IX monomethyl ester cyclase, Elongator protein 3/MiaB/NifB family

MSM0386 sodium/proline symporter (proline permease), PutP

MSM0387 coenzyme F390 synthetase, PaaK

MSM0388 amino acid regulator

MSM0389 hypothetical protein

MSM0390 hypothetical protein

MSM0391 indolepyruvate ferredoxin oxidoreductase, beta subunit

MSM0392 indolepyruvate ferredoxin oxidoreductase, alpha subunit

MSM0393 fumarate reductase, iron-sulfur protein

MSM0394 rRNA methylase, SpoU family

MSM0395 ferredoxin, iron-sulfur binding

MSM0396 putative transposase

MSM0397 xanthine/uracil permease, UraA

MSM0398 uracil phosphoribosyltransferase, Upp

MSM0399 hypothetical protein

MSM0400 hypothetical protein

MSM0401 predicted surface protease

MSM0402 dCTP deaminase, dUTPase family

MSM0403 glycyl-tRNA synthetase

MSM0404 predicted transcriptional regulator

MSM0405 predicted metal-dependent DNase, TatD-related family

MSM0406 conserved hypothetical protein

MSM0407 P-loop containing nucleoside triphosphate hydrolase (NAD(P)- binding)

MSM0408 2-phosphoglycerate kinase/small-molecule binding protein

MSM0409 C4-type Zinc-finger protein

MSM0410 conserved hypothetical protein, histone-fold superfamily

MSM0411 adhesin-like protein

MSM0412 putative adhesin-like protein

MSM0413 transcriptional regulator, MarR family

MSM0414 Na+-driven multidrug efflux pump, NorM

MSM0415 uridylate kinase, PyrH

MSM0416 Mg-dependent DNase, TatD-related

MSM0417 predicted transmembrane protein with a zinc ribbon

MSM0418 conserved hypothetical protein

MSM0419 conserved hypothetical protein

MSM0420 predicted permease

MSM0421 hypothetical protein

MSM0422 conserved hypothetical membrane protein

MSM0423 glycosyltransferase (modular protein with two domains distantly related to glycosyltransferases), GT2/GT1 families [CAZy]

MSM0424 transcription initiator factor TFIIB (zinc-binding)

MSM0425 predicted RNA-binding protein involved in rRNA processing

MSM0426 demethylmenaquinone methyltransferase

MSM0427 DNA primase (bacterial type), DnaG

MSM0428 integrase-recombinase protein, phage integrase family

MSM0429 biotin biosynthesis protein, BioY

MSM0430 conserved hypothetical protein, predicted metal-binding

MSM0431 predicted ATP-dependent carboligase, biotin carboxylase-related

MSM0432 conserved hypothetical protein

MSM0433 archaeal/vacuolar-type H+-transporting ATP synthase, subunit D

MSM0434 archaeal/vacuolar-type H+-transporting ATP synthase, subunit B

MSM0435 archaeal/vacuolar-type H+-transporting ATP synthase, subunit A

MSM0436 archaeal/vacuolar-type H+-transporting ATP synthase, subunit F

MSM0437 archaeal/vacuolar-type H+-transporting ATP synthase, subunit C

MSM0438 archaeal/vacuolar-type H+-transporting ATP synthase, subunit E

MSM0439 archaeal/vacuolar-type H+-transporting ATP synthase, subunit K

MSM0440 archaeal/vacuolar-type H+-transporting ATP synthase, subunit I

MSM0441 archaeal/vacuolar-type H+-transporting ATP synthase, subunit H

MSM0442 hypothetical protein

MSM0443 hypothetical protein

MSM0444 hypothetical protein

MSM0445 NADH dehydrogenase/NAD(P)H nitroreductase

MSM0446 citrate synthase, GltA

MSM0447 fumarate hydratase, alpha subunit

MSM0448 conserved hypothetical protein

MSM0449 2-methylcitrate dehydratase, MmgE/PrpD family

MSM0450 conserved hypothetical membrane protein

MSM0451 conserved hypothetical membrane protein

MSM0452 predicted DNA-binding protein

MSM0453 predicted transcriptional regulator

MSM0454 hypothetical protein

MSM0455 conserved hypothetical protein

MSM0456 conserved hypothetical protein

MSM0457 D-3-phosphoglycerate dehydrogenase, SerA

MSM0458 transposase, homeodomain-like superfamily ND

MSM0459 hypothetical protein

MSM0460 predicted transposase

MSM0461 adhesion-like protein

MSM0462 predicted metal-dependent protease, PAD1/JAB1 superfamily

MSM0463 predicted tRNA (His) guanylyltransferase

MSM0464 homoserine/aspartate dehydrogenase (NAD binding), glyceraldehyde-3-phosphate dehydrogenase-like superfamily

MSM0465 conserved hypothetical protein

MSM0466 predicted tRNA-binding protein

MSM0467 NADP-dependent glyceraldehyde-3-phosphate dehydrogenase

MSM0468 conserved hypothetical membrane protein

MSM0469 conserved hypothetical membrane protein

MSM0470 conserved hypothetical membrane protein

MSM0471 type II secretion system protein F, GspF

MSM0472 Xaa-Pro aminopeptidase

MSM0473 hypothetical protein

MSM0474 hypothetical protein

MSM0475 hypothetical protein

MSM0476 hypothetical protein

MSM0477 hypothetical protein

MSM0478 hypothetical protein

MSM0479 Zn-dependent protease, peptidase M50 family

MSM0480 YcaO-like protein

MSM0481 TfuA-like protein

MSM0482 ATP-utilizing enzymes, PP-loop superfamily

MSM0483 conserved hypothetical protein

MSM0484 inosine-5′-monophosphate dehydrogenase related protein

MSM0485 universal stress protein, UspA

MSM0486 N-ethylammeline chlorohydrolase, metallo-dependent amidohydrolase family

MSM0487 hypothetical protein

MSM0488 carbamoylphosphate synthase, large subunit, CarB

MSM0489 carbamoylphosphate synthase, small subunit, CarA

MSM0490 SAM-dependent methyltransferase, UbiE/CobQ family

MSM0491 nicotinate-nucleotide pyrophosphorylase (carboxylating), NadC

MSM0492 ribonuclease Z (zinc-dependent), beta-lactamase superfamily, ElaC

MSM0493 mechanosensitive ion channel protein, Sm-like ribonucleoprotein superfamily, MscS

MSM0494 quiinolinate synthetase, subunit A, NadA

MSM0495 conserved hypothetical protein

MSM0496 homoserine O-acetyltransferase

MSM0497 predicted nuclease, RecB family

MSM0498 hypothetical protein

MSM0499 conserved hypothetical protein

MSM0500 N-carbamoyl-D-amino acid amidohydrolase

MSM0501 phycocyanin alpha phycocyanobilin lyase, CpcE

MSM0502 ATP-depepndent helicase, Lhr-like

MSM0503 flavodoxin, FldA

MSM0504 conserved hypothetical protein

MSM0505 hypothetical protein

MSM0506 ATP-utilizing enzyme, ATP-grasp superfamily

MSM0507 predicted phosphoesterase, YfcE

MSM0508 cell division protein J (23S rRNA methlase), FtsJ

MSM0509 conserved hypothetical protein

MSM0510 predicted ATPase involved in DNA replication control, MCM2/3/5 family

MSM0511 translation initiator factor 2, beta subunit (alF-2beta)

MSM0512 NMD3-related protein (nonsense mediated mRNA decay)

MSM0513 tyrosyl-tRNA synthetase, TyrS

MSM0514 conserved hypothetical protein

MSM0515 methanol:cobalamin methyltransferase, MtaB

MSM0516 corrinoid protein (methionine synthase-related), MtaC

MSM0517 methyltransferase activation protein, MapA

MSM0518 methylcobalamin:coenzyme M methyltransferase, MtaA

MSM0519 conserved hypothetical protein

MSM0520 thymidylate kinase, Tmk

MSM0521 conserved hypothetical membrane protein

MSM0522 collagenase, peptidase family U32

MSM0523 collagenase, peptidase family U32

MSM0524 DNA mismatch repair ATPase, MutS

MSM0525 predicted unusual protein kinase, ubiquinone biosynthesis protein- related, AarF

MSM0526 conserved hypothetical protein

MSM0527 IS element ISM1 (ICSNY family)

MSM0528 IS element ISM1 (ICSNY family)

MSM0529 hypothetical protein

MSM0530 predicted O-linked GlcNAc transferase

MSM0531 adenine/cytosine DNA methyltransferase

MSM0532 IS element ISM1 (ICSNY family)

MSM0533 IS element ISM1 (ICSNY family)

MSM0534 IS element ISM1 (ICSNY family)

MSM0535 hypothetical protein

MSM0536 hypothetical protein

MSM0537 TPR-repeat protein

MSM0538 pyruvate formate-lyase activating enzyme, PflA

MSM0539 putative DNA-directed DNA polymerase

MSM0540 predicted transcriptional regulator

MSM0541 hypothetical protein ND

MSM0542 coenzyme F420-dependent N5, N10-methylene tetrahydromethanopterin

MSM0543 DNA repair photolyase, SplB

MSM0544 predicted Fe-S oxidoreductase

MSM0545 conserved hypothetical protein

MSM0546 conserved hypothetical protein

MSM0547 predicted nucleotidyltransferase, cytidyltransferase-related

MSM0548 6-phosphogluconate dehydrogenase, beta-hydroxyacid dehydrogenase related, MmsB

MSM0549 cytochrome C-type biogenesis protein, DsbD

MSM0550 protein disulfide-isomerase, thioredoxin-related

MSM0551 conserved hypothetical protein

MSM0552 sulfur transfer protein involved in thiamine biosynthesis

MSM0553 ATPase, PP-loop superfamily

MSM0554 protein containing von Willebrand factor type A (vWA) domain, CoxE

MSM0555 MoxR-like ATPase

MSM0556 dihydropteroate synthase

MSM0557 pyruvate:ferredoxin oxidoreductase, gamma subunit, PorG

MSM0558 pyruvate:ferredoxin oxidoreductase, delta subunit, PorD

MSM0559 pyruvate:ferredoxin oxidoreductase, alpha subunit, PorA

MSM0560 pyruvate:ferredoxin oxidoreductase, beta subunit, PorB

MSM0561 formate dehydrogenase, iron-sulfur subunit

MSM0562 formate dehydrogenase, iron-sulfur subunit

MSM0563 fumarate hydratease, alpha subunit

MSM0564 phosphate uptake regulator, PhoU

MSM0565 phosphate ABC transporter, ATPase component, PstB

MSM0566 phosphate ABC transporter, permease component, PstA

MSM0567 phosphate ABC transporter, permease component, PstC

MSM0568 phosphate ABC transporter, phosphate-binding component, PstS

MSM0569 phosphate transport system regulator related protein, PhoU

MSM0570 conserved hypothetical protein

MSM0571 conserved hypothetical protein

MSM0572 H2-forming N5, N10-methylenetetrahydromethanopterin dehydrogenase (coenzyme F420-dependent), Mth

MSM0573 biotin synthetase, BioB

MSM0574 conserved hypothetical protein

MSM0575 conserved hypothetical protein

MSM0576 NIF3-related protein (NGG1p interacting factor 3)

MSM0577 predicted dinucleotide-utilizing enzyme, ThiF/HesA family

MSM0578 conserved hypothetical protein

MSM0579 polyferredoxin, iron-sulfur binding

MSM0580 putative adhesin-like protein

MSM0581 conserved hypothetical membrane protein

MSM0582 peptide methionine sulfoxide reductase, PMSR

MSM0583 cobalt ABC transporter, permease component, CbiM

MSM0584 cobalt ABC transporter, permease component

MSM0585 cobalt ABC transporter, permease component, CbiQ

MSM0586 cobalt ABC transporter, ATPase component, CbiO

MSM0587 conserved hypothetical protein

MSM0588 ferrous iron transport protein A, FeoA

MSM0589 ferrous iron transport protein B, FeoB

MSM0590 hypothetical protein

MSM0591 hypothetical protein

MSM0592 conserved hypothetical protein

MSM0593 multidrug ABC transporter, ATPase component, CcmA

MSM0594 multidrug ABC transporter, permease component

MSM0595 multidrug ABC transporter, permease component

MSM0596 bacterial type II secretion system protein, GspF

MSM0597 bacterial type II/IV secretion system protein kinase, GspE

MSM0598 SAM-dependent methyltransferase

MSM0599 conserved hypothetical membrane protein

MSM0600 transcriptional regulator, MarR family

MSM0601 putative transposase ND MSM0602 translation elongation factor EF-1, beta subunit

MSM0603 predicted Zn-ribbon RNA-binding protein involved in translation

MSM0604 predicted archaeal aspartate/glutamate/uridylate kinase

MSM0605 peptidyl-tRNA hydrolase, PTH2 family

MSM0606 hypothetical protein

MSM0607 predicted ATPase, RNase L inhibitor family

MSM0608 putative metal-binding protein

MSM0609 ferredoxin, iron-sulfur binding

MSM0610 aspartate aminotransferase

MSM0611 DNA repair protein, RadB

MSM0612 putative translation factor, Sua5/YciO/YrdC/YwlC family

MSM0613 phosphatidylglycerophosphate synthase, PgsA

MSM0614 conserved hypothetical protein

MSM0615 archaeal fructose 1,6-bisphosphatase

MSM0616 adhesin-like protein

MSM0617 thiamine biosynthesis ATP pyrophosphatase, Thil

MSM0618 pH regulator (monovalent cation:H+antiporter

MSM0619 alanyl-tRNA synthetase, AlaS

MSM0620 ribosomal protein L12p

MSM0621 ribosomal protein L10p

MSM0622 ribosomal protein L1p

MSM0623 ribosomal protein L11

MSM0624 transcription antiterminator, NusG

MSM0625 protein translocation complex sec61, gamma subunit

MSM0626 cell division protein, FtsZ

MSM0627 tetrahydromethanopterin S-methyltransferase, subunit H, MtrH

MSM0628 conserved hypothetical protein

MSM0629 putative transposase ND

MSM0630 conserved hypothetical protein

MSM0631 transcription initiator factor IIE, alpha unit

MSM0632 predicted hydrolase, HD superfamily

MSM0633 archaeosine tRNA-ribosyltransferase

MSM0634 predicted metal-sulfur cluster biosynthetic enzyme

MSM0635 predicted regulator of amino acid metabolism

MSM0636 hydrogenase expression/formation protein, HypC

MSM0637 dihydrolipoamide dehydrogenase

MSM0638 pfam match to MurG; not predicted to be a carbohydrate active enzyme by CAZy

MSM0639 putative cell wall biosynthesis protein

MSM0640 cell division protein (RNA-binding), PeIA

MSM0641 prephenate dehydrogenase (NADP+)

MSM0642 cell divison control protein Cdc48, AAA+ATPase family

MSM0643 conserved hypothetical protein

MSM0644 thiamine biosynthesis protein, ThiC

MSM0645 ATP-dependent DNA ligase, Cdc9

MSM0646 conserved hypothetical protein

MSM0647 predicted RNA-binding protein, contains TRAM domain

MSM0648 phosphomannomutase, ManB

MSM0649 conserved hypothetical protein

MSM0650 transcriptional regulator, TetR/AcrR family

MSM0651 best blast hit to MTH 1585; not predicted to be a carbohydrate active enzyme by CAZy

MSM0652 pyruvate formate-lyase activating enzyme, PflA

MSM0653 histidinol-phosphate aminotransferase, HisC

MSM0654 carbonic anhydrase, Cab

MSM0655 glucose-1-phosphate thymidylyltransferase

MSM0656 phosphomannomutase, ManB

MSM0657 phosphoglycerate mutase, AP superfamily

MSM0658 hypothetical protein

MSM0659 conserved hypothetical membrane protein

MSM0660 LemA protein

MSM0661 small subunit ribosomal protein S3Ae

MSM0662 putative flagellar protein, FliL

MSM0663 dinitrogenase iron-molybdenum cofactor biosynthesis protein, NifX_NifB family

MSM0664 multimeric flavodoxin, NADPH-dependent FMN reductase family

MSM0665 5′-methylthioadenosine phosphorylase

MSM0666 conserved hypothetical protein

MSM0667 conserved hypothetical protein

MSM0668 conserved hypothetical protein

MSM0669 hypothetical protein

MSM0670 conserved hypothetical protein

MSM0671 cell division control protein Cdc6-related, AAA+ATPase superfamily

MSM0672 thiamine pyrophosphokinase

MSM0673 conserved hypothetical membrane protein

MSM0674 hypothetical protein

MSM0675 hypothetical protein

MSM0676 conserved hypothetical membrane protein

MSM0677 archaeal aspartate aminotransferase

MSM0678 conserved hypothetical membrane protein

MSM0679 conserved hypothetical membrane protein

MSM0680 predicted ATPase, AAA+ superfamily

MSM0681 conserved hypothetical protein

MSM0682 hypothetical protein

MSM0683 conserved hypothetical protein

MSM0684 conserved hypothetical protein

MSM0685 hypothetical protein

MSM0686 acetolactate synthase (TPP-requiring), large subunit, IIvB

MSM0687 deoxycytidine-triphosphate deaminase, Dcd

MSM0688 4-oxalocrotonate tautomerase

MSM0689 hypothetical protein

MSM0690 helicase

MSM0691 mutator mutT protein (NUDIX domain)

MSM0692 conserved hypothetical protein

MSM0693 ATPase involved in DNA repair, SbcC

MSM0694 hypothetical protein

MSM0695 DNA repair helicase

MSM0696 Fe-S oxidoreductase

MSM0697 hypothetical protein

MSM0698 hypothetical protein

MSM0699 Na+-dependent transporter, SNF family

MSM0700 putative poly-gamma-glutamate synthesis protein, PgsA

MSM0701 signal recognition particle GTPase SRP54

MSM0702 predicted prefoldin, alpha subunit

MSM0703 ribosomal protein LX

MSM0704 translation initiation factor 6 (alF-6)

MSM0705 ribosomal protein L31a

MSM0706 ribosomal protein L39a

MSM0707 predicted subunit of tRNA methyltransferase

MSM0708 dsDNA-binding protein

MSM0709 ribosomal protein S16a

MSM0710 RNA-binding protein, CRS1/YhbY family

MSM0711 ribonuclease P, subunit RPR2

MSM0712 conserved hypothetical protein (DUF1696 domain)

MSM0713 predicted nucleotide kinase

MSM0714 predicted GTPase

MSM0715 predicted GTPase

MSM0716 oligosaccharyl transferase, STT3 subunit

MSM0717 DNA topoisomerase I, TopA

MSM0718 conserved hypothetical protein

MSM0719 phosphoserine phosphatase, HAD family, SerB

MSM0720 transcription initiator factor TFIID TATA binding protein

MSM0721 adenylate cyclase, class 2

MSM0722 2-isopropylmalate synthase, LeuA

MSM0723 3-isopropylmalate dehydratase, LeuC

MSM0724 4-hydroxybenzoate synthetase (chorismate lyase)

MSM0725 DNA repair flap structure-specific 5′-3′ endonuclease

MSM0726 conserved hypothetical protein

MSM0727 S-adenosylhomocysteine hydrolase (adenosylhomocysteinase), AhcY

MSM0728 predicted oxidoreductase, aldo/keto reductase family

MSM0729 molybdopterin biosynthesis protein, MoeB

MSM0730 putative transposase ND MSM0731 putative DNA helicase II, UvrD

MSM0732 tRNA pseudouridine synthase B, TruB

MSM0733 ribosomal protein L14e

MSM0734 cytidylate kinase, Cmk

MSM0735 ribosomal protein L34e

MSM0736 conserved hypothetical membrane protein

MSM0737 archaeal adenylate kinase, AdkA

MSM0738 preproetin translocase, SecY subunit, SecY

MSM0739 ribosomal protein L15p

MSM0740 ribosomal protein L30p

MSM0741 ribosomal protein S5p, RpsE

MSM0742 ribosomal protein L18p, RpIR

MSM0743 ribosomal protein L19e

MSM0744 ribosomal protein L32e

MSM0745 ribosomal protein L6p, RpIF

MSM0746 ribosomal protein S8p

MSM0747 ribosomal protein S14p

MSM0748 ribosomal protein L5p

MSM0749 ribosomal protein S4e

MSM0750 ribosomal protein L24p

MSM0751 ribosomal protein L14p

MSM0752 ribosomal protein S17p

MSM0753 ribonuclease P, subunit P29

MSM0754 translation initiation factor SUI1

MSM0755 ribosomal protein L29p

MSM0756 ribosomal protein S3p

MSM0757 ribosomal protein L22p

MSM0758 ribosomal protein S19p

MSM0759 ribosomal protein L2p

MSM0760 ribosomal protein L23p

MSM0761 ribosomal protein L1e

MSM0762 ribosomal protein L3p

MSM0763 conserved hypothetical protein

MSM0764 ribosomal L11 RNA methyltransferase (SAM-dependent)

MSM0765 pyruvate carboxylase (acetyl-CoA/biotin carboxylase), subunit A, PycA

MSM0766 biotin-[acetyl-CoA-carboxylase]ligase/biotin operon regulator bifunctional protein, BirA

MSM0767 selenocysteine synthase, SelA

MSM0768 conserved hypothetical protein

MSM0769 fumarate hydratase, class I

MSM0770 cobalt ABC transporter, ATPase component, CbiO

MSM0771 cobalt ABC transporter, permease component, CbiQ

MSM0772 predicted permease, major facilitator superfamily

MSM0773 multidrug ABC transporter, ATPase component

MSM0774 multidrug ABC transporter, ATPase component

MSM0775 transcriptional regulator, AraC family

MSM0776 conserved hypothetical membrane protein

MSM0777 conserved hypothetical protein

MSM0778 predicted RNA-binding protein, eukaryotic snRNP-like

MSM0779 predicted Zn-dependent hydrolase, metallo-beta-lactamase superfamily

MSM0780 conserved hypothetical protein

MSM0781 conserved hypothetical protein

MSM0782 hypothetical protein

MSM0783 tungsten formylmethanofuran dehydrogenase, subunit F, FwdF

MSM0784 ferredoxin

MSM0785 predicted phosphopantetheine adenylyltransferase (PPAT)

MSM0786 transglutaminase-like protein, putative cysteine protease

MSM0787 Fe-S oxidoreductase

MSM0788 aspastate aminotransferase

MSM0789 cation efflux system protein (zinc/cadmium/cobalt)

MSM0790 CBS-domain-containing protein

MSM0791 2-phosphoglycerate kinase

MSM0792 predicted calcineurin-like phosphoesterase

MSM0793 conserved hypothetical protein

MSM0794 conserved hypothetical protein

MSM0795 heterodisulfide reductase, subunit B, HdrB

MSM0796 heterodisulfide reductase, subunit C, HdrC

MSM0797 archaeosine tRNA-ribosyltransferase

MSM0798 hypothetical protein

MSM0799 conserved hypothetical protein

MSM0800 hypothetical protein

MSM0801 diphthine synthase, DphB

MSM0802 methyltransferase

MSM0803 predicted metal-dependent membrane protease, CAAX amino terminal protease family

MSM0804 translation initiation factor alF-2B, alpha subunit

MSM0805 polar amino acid ABC transporter, ATPase component

MSM0806 polar amino acid ABC transporter, permease component

MSM0807 polar amino acid ABC transporter, substrate-binding component

MSM0808 nitrogenase iron-molybdenum cofactor biosynthesis protein, NifB

MSM0809 conserved hypothetical protein

MSM0810 activator of (R)-2-hydroxyglutaryl-CoA dehydratase

MSM0811 conserved hypothetical protein

MSM0812 conserved hypothetical protein

MSM0813 predicted peptidyl-prolyl cis-trans isomerase

MSM0814 phosphoribosylformylglycinamidine synthase-related protein (selenophosphate synthetase)

MSM0815 conserved hypothetical protein

MSM0816 predicted nucleic acid-binding protein, PIN domain-like family

MSM0817 predicted transcriptional regulator

MSM0818 predicted transcriptional regulator

MSM0819 putative transcription regulator, ArsR family

MSM0820 molybdenum cofactor biosynthesis protein, MoaB

MSM0821 orotate phosphoribosyltransferase, PyrE

MSM0822 photosynthetic reaction centre cytoplasmic domain-containing protein

MSM0823 phosphoenolpyruvate synthase/pyruvate phosphate dikinase, PpsA

MSM0824 putative N-acetyltransferase, GNAT family

MSM0825 adenosylcobinamide amidohydrolase, CbiZ

MSM0826 chaperonin, Cpn60/TCP-1/thermosome family, GroL

MSM0827 predicted metal-dependent hydrolase, cyclase family

MSM0828 best blast hit to Msp_0220; not predicted to be a carbohydrate active enzyme by CAZy

MSM0829 aspartate-semialdehyde dehydrogenase, Asd

MSM0830 dihydrodipicolinate reductas, DapB

MSM0831 dihydrodipicolinate synthase, DapA

MSM0832 aspartokinase, alpha subunit

MSM0833 ribosomal protein S17a

MSM0834 chorismate mutase

MSM0835 archaeal shikimate kinase

MSM0836 related to alpha-glycosyltransferases, GT4 family

MSM0837 cobalamin biosynthesis protein D, CbiD

MSM0838 putative thioredoxin/glutaredoxin

MSM0839 ATP-dependent helicase

MSM0840 conserved hypothetical protein

MSM0841 photosynthetic reaction centre cytoplasmic domain containing protein

MSM0842 histone acetyltransferase, radical SAM superfamily

MSM0843 2-deoxyribose-5-phosphate aldolase (DERA), DeoC

MSM0844 archaeal histone, HmtA

MSM0845 2-methylthioadenine synthetase, MiaB

MSM0846 uncharacterized archaeal Zn-finger protein

MSM0847 archaeal 3-isopropylmalate dehydratase, small subunit, LeuD

MSM0848 ribofuranosylaminobenzene 5′-phosphate synthase, RfaS

MSM0849 molybdenum cofactor biosynthesis-related protein, MoaA

MSM0850 predicted CDP-diglyceride synthetase

MSM0851 predicted transcriptional regulator

MSM0852 predicted ATP-utilizing enzyme

MSM0853 UDP-N-acetylglucosamine 2-epimerase, WecB

MSM0854 hypothetical protein

MSM0855 archaeal tRNA pseudouridine synthase A, TruA

MSM0856 antimicrobial peptide ABC transporter, permease component

MSM0857 antimicrobial peptide ABC transporter, ATPase component

MSM0858 phosphoribosylformimino-5-aminoimidazole carboxamide ribotide (ProFAR)isomerase, HisA

MSM0859 glycerol-3-phosphate cytidylyltransferase

MSM0860 aspartate-semialdehyde dehydrogenase, ArgC

MSM0861 flavodoxin

MSM0862 aspartate carbamoyltransferase regulatory chain, PyrI

MSM0863 pyridoxamine-phosphate oxidase (FMN-binding)

MSM0864 predicted transcriptional regulator

MSM0865 putative glucose-methanol-choline oxidoreductase (FAD-dependent)

MSM0866 Zn metalloprotease, TIdD

MSM0867 AMMECR1-related protein

MSM0868 hypothetical protein

MSM0869 GTPase, GTP1/OBG family

MSM0870 molecular chaperone (small heat shock protein), HSP20/alpha crystallin family

MSM0871 putative transposase ND

MSM0872 glucosamine:fructose-6-phosphate aminotransferase (isomerizing), AgaS

MSM0873 conserved hypothetical protein

MSM0874 adenine deaminase, AdeC

MSM0875 lysine-oxoglutarate reductase/Saccharopine dehydrogenase (LOR/SDH) bifunctional enzyme

MSM0876 arginase/agmatinase/formimionoglutamate hydrolase, SpeB

MSM0877 translation initiation factor 5A (alF-5A)

MSM0878 pyruvoyl-dependent arginine decarboxylase, PdaD

MSM0879 Poly(P)/ATP NAD kinase, inositol monophosphatase family, PpnL

MSM0880 UDP-N-acetylmuramyl tripeptide synthetase (Mur ligase)

MSM0881 porphobilinogen deaminase

MSM0882 3-chlorobenzoate-3,4-dioxygenase dyhydrogenase

MSM0883 orotate phosphoribosyltransferase

MSM0884 adhesin-like protein

MSM0885 adhesin-like protein

MSM0886 hypothetical protein

MSM0887 universal stress protein, adenine nucleotide alpha hydrolase-like family

MSM0888 glutamate dehydrogenase (NADP+), GdhA

MSM0889 hypothetical protein

MSM0890 hypothetical protein

MSM0891 peptide chain release factor eRF, subunit 1

MSM0892 putative zinc-binding protein

MSM0893 acetyltransferase

MSM0894 conserved hypothetical protein

MSM0895 cation transport ATPase, HAD family

MSM0896 precorrin-6X reductase, CbiJ

MSM0897 ribosomal protein S10p

MSM0898 translation elongation factor 1-alpha (EF-Tu)

MSM0899 translation elongation factor EF-2, FusA

MSM0900 ribosomal protein S7p

MSM0901 ribosomal protein S12p

MSM0902 methyl-coenzyme M reductase, alpha subunit, McrA

MSM0903 methyl-coenzyme M reductase, gamma subunit, McrG

MSM0904 methyl-coenzyme M reductase, D subunit, McrD

MSM0905 methyl-coenzyme M reductase, beta subunit, McrB

MSM0906 transcription termination factor, NusA

MSM0907 ribosomal protein L17Ae

MSM0908 DNA-dependent RNA polymerase, subunit A, RpoA

MSM0909 DNA-dependent RNA polymerase, subunit A′, RpoA

MSM0910 DNA-dependent RNA polymerase, subunit B′, RpoB

MSM0911 DNA-dependent RNA polymerase, subunit B, RpoB

MSM0912 DNA-dependent RNA polymerase, subunit H, RpoH

MSM0913 hypothetical protein

MSM0914 predicted O-linked GlcNAc transferase

MSM0915 hypothetical protein

MSM0916 hydroxyethylthiazole kinase, ThiM

MSM0917 thiamine monophosphate synthase, ThiE

MSM0918 3-phosphoglycerate kinase, Pgk

MSM0919 triosephosphate isomerase, TpiA

MSM0920 conserved hypothetical protein

MSM0921 predicted surface protein

MSM0922 Fe-S oxidoreductase

MSM0923 multimeric flavodoxin

MSM0924 succinyl-CoA synthetase, beta subunit, SucC

MSM0925 2-oxoglutarate ferredoxin oxidoreductase, gamma subunit, KorC

MSM0926 2-oxoglutarate ferredoxin oxidoreductase, beta subunit, KorB

MSM0927 2-oxoglutarate ferredoxin oxidoreductase, alpha subunit, KorA

MSM0928 2-oxoglutarate ferredoxin oxidoreductase, delta subunit, KorD

MSM0929 fumarate hydratase, FumA

MSM0930 peptidyl-prolyl cis-trans isomerase, FKBP-type

MSM0931 conserved hypothetical protein

MSM0932 conserved hypothetical protein

MSM0933 cobalamin-5-phosphate synthase, CobS

MSM0934 predicted phosphatidylglycerophosphatase A-related protein

MSM0935 conserved hypothetical protein

MSM0936 transcription regulator-related ATPase, ExsB

MSM0937 HD superfamily hydrolase

MSM0938 hypothetical protein

MSM0939 pyruvate carboxylase, subunit B, PycB

MSM0940 myo-inositol-1-phosphate synthase

MSM0941 prenylteansferase, UbiA

MSM0942 conserved hypothetical membrane protein

MSM0943 conserved hypothetical protein

MSM0944 CMP-N-acetylneuraminic acid synthetase, NeuA

MSM0945 hydrogenase expression/formation protein, HypD

MSM0946 archaeal sucrose-phosphate phosphatase (SPP-like), HAD family

MSM0947 predicted zinc metalloprotease, modulator of DNA gyrase

MSM0948 hypothetical protein

MSM0949 transcriptional activator

MSM0950 molybdopterin biosynthesis protein, MoeA

MSM0951 translation initiation factor alF-1A

MSM0952 serine/threonine protein kinase, RIO1 family

MSM0953 conserved hypothetical membrane protein

MSM0954 predicted RNA-binding protein

MSM0955 type II DNA topoisomerase VI, subunit B

MSM0956 type II DNA topoisomerase VI, subunit A

MSM0957 adhesin-like protein

MSM0958 predicted 1,4-beta-cellobiosidase

MSM0959 conserved hypothetical protein

MSM0960 cation transport ATPase, HAD family

MSM0961 heavy-metal cation transporting ATPase

MSM0962 glyceraldehyde 3-phosphate dehydrogenase, GapA

MSM0963 endonuclease IV, xylose isomerase-like TIM barrel family, Nfo

MSM0964 calcineurin-like phosphoesterase

MSM0965 3-hydroxyacyl-CoA dehydrogenase, FadB

MSM0966 predicted 26S protease regulatory subunit (ATP-dependent), AAA+ family ATPase

MSM0967 glutamyl-tRNA reductase, HemA

MSM0968 bifunctional precorrin-2 oxidase/chelatase (siroheme synthase), CysG

MSM0969 predicted metal-binding transcription factor

MSM0970 conserved hypothetical protein

MSM0971 methyl-coenzyme M reductase, component A2

MSM0972 tRNA-dihydrouridine synthase

MSM0973 GTP cyclohydrolase III, GGDN family

MSM0974 LPPG:FO 2-phospho-L-lactate transferase, CofD

MSM0975 F420-0:gamma-glutamyl ligase, CofE

MSM0976 archaeal IMP cyclohydrolase, PurO

MSM0977 putative biopolymer transport protein, ExbD/TolR family

MSM0978 biopolymer transport protein, MotA/TolQ/ExbB proton channel family

MSM0979 ribonuclease HII, RnhB

MSM0980 rod shape-determining protein, MreB/MrI family

MSM0981 conserved hypothetical protein

MSM0982 phosphatidylserine synthase, PssA

MSM0983 conserved hypothetical protein

MSM0984 sortase (surface protein transpeptidase), SrtA

MSM0985 conserved hypothetical protein

MSM0986 conjugated bile acid hydrolase (CBAH)

MSM0987 tyrosine decarboxylase, MfnA

MSM0988 phosphoenolpyruvate synthase, PpsA

MSM0989 ribosomal protein L10e

MSM0990 nitrate/sulfonate/bicarbonate ABC transporter, ATPase component

MSM0991 nitrate/sulfonate/bicarbonate ABC transporter, substrate-binding component

MSM0992 conserved hypothetical protein

MSM0993 putative ATPase, glucocorticoid receptor-like (DNA-binding domain) family

MSM0994 predicted nucleotidyltransferase

MSM0995 adhesin-like protein

MSM0996 adhesin-like protein

MSM0997 dihydroorotase, PyrC

MSM0998 polyferredoxin, MvhB

MSM0999 methyl viologen-reducing hydrogenase, alpha subunit, MvhA

MSM1000 methyl viologen-reducing hydrogenase, gamma subunit, MvhG

MSM1001 methyl viologen-reducing hydrogenase, delta subunit, MvhD P

MSM1002 ABC transporter involved in Fe-S cluster assembly, permease component

MSM1003 ABC transporter involved in Fe-S cluster assembly, permease component

MSM1004 photosynthetic reaction centre cytoplasmic domain containing protein

MSM1005 GTP:adenosylcobinamide-phosphate guanylyltransferase

MSM1006 conserved hypothetical protein

MSM1007 N5-methyl-tetrahydromethanopterin:coenzyme M methyltransferase, subunit H, MtrH

MSM1008 N5-methyl-tetrahydromethanopterin:coenzyme M methyltransferase, subunit G, MtrG

MSM1009 N5-methyl-tetrahydromethanopterin:coenzyme M methyltransferase, subunit F, MtrF

MSM1010 N5-methyl-tetrahydromethanopterin:coenzyme M methyltransferase, subunit A, MtrA

MSM1011 N5-methyl-tetrahydromethanopterin:coenzyme M methyltransferase, subunit B, MtrB

MSM1012 N5-methyl-tetrahydromethanopterin:coenzyme M methyltransferase, subunit C, MtrC

MSM1013 N5-methyl-tetrahydromethanopterin:coenzyme M methyltransferase, subunit D, MtrD

MSM1014 N5-methyl-tetrahydromethanopterin:coenzyme M methyltransferase, subunit E, MtrE

MSM1015 methyl-coenzyme M reductase, alpha subunit, McrA

MSM1016 methyl-coenzyme M reductase, gamma subunit, McrG

MSM1017 methyl-coenzyme M reductase, C subunit, McrC

MSM1018 methyl-coenzyme M reductase, D subunit, McrD

MSM1019 methyl-coenzyme M reductase, beta subunit, McrB

MSM1020 Fe-S oxidoreductase, Radical SAM family

MSM1021 uncharacterized protein related to methyl coenzyme M reductase subunit C (McrC)

MSM1022 conserved hypothetical protein

MSM1023 2-phosphosulpholactate phosphatase, ComB, (coenzyme M biosynthesis)

MSM1024 pheromone shutdown protein, traB family

MSM1025 conserved hypothetical protein

MSM1026 hemolysin-related protein, transporter-associated family, TlyC

MSM1027 Ca2+/Na+antiporter (K+-dependent)

MSM1028 predicted ATPase, PP-loop family

MSM1029 conserved hypothetical protein

MSM1030 predicted pyridoxal phosphate-dependent enzyme

MSM1031 N2,N2-dimethylguanosine tRNA methyltransferase, Trm1

MSM1032 transcriptional regulator, Lrp family

MSM1033 conserved hypothetical protein

MSM1034 conserved hypothetical protein

MSM1035 FO synthase subunit 1 (SAM-dependent), CofG (F420 biosynthesis)

MSM1036 predicted methyltransferase

MSM1037 proteasome, beta subunit

MSM1038 predicted metal-dependent RNase

MSM1039 phosphoribosylformylglycinamidine cyclo-ligase (AIRS), PurM

MSM1040 malate/L-lactate dehydrogenase

MSM1041 DNA-dependent DNA polymerase I, PolB1

MSM1042 predicted permease

MSM1043 dihydroorotate dehydrogenase electron transfer subunit, PyrK

MSM1044 dihydroorotate dehydrogenase, PyrD

MSM1045 possible glycosyltransferase

MSM1046 pre-mRNA splicing ribonucleoprotein PRP31

MSM1047 fibrillarin-like pre-rRNA processing protein, FlpA

MSM1048 phosphopantothenoylcysteine synthetase/decarboxylase

MSM1049 phosphopantothenoylcysteine synthetase/decarboxylase

MSM1050 conserved hypothetical protein

MSM1051 putative endoglucanase

MSM1052 prephenate dehydratase, PheA

MSM1053 IMP dehydrogenase related protein

MSM1054 IMP dehydrogenase related protein

MSM1055 coenzyme PQQ synthesis protein, SAM family

MSM1056 6-pyruvoyl-tetrahydropterin synthase

MSM1057 conserved hypothetical protein

MSM1058 conserved hypothetical protein

MSM1059 predicted RecB family exonuclease

MSM1060 energy-converting hydrogenase B, subunit Q, EhbQ

MSM1061 energy-converting hydrogenase B, subunit P, EhbP

MSM1062 energy-converting hydrogenase B, subunit O, EhbO

MSM1063 energy-converting hydrogenase B, subunit N, EhbN

MSM1064 energy-converting hydrogenase B, subunit M, EhbM

MSM1065 energy-converting hydrogenase B, subunit L, EhbL

MSM1066 energy-converting hydrogenase B, subunit K, EhbK

MSM1067 energy-converting hydrogenase B, subunit J, EhbJ

MSM1068 energy-converting hydrogenase B, subunit I, EhbI

MSM1069 energy-converting hydrogenase B, subunit H, EhbH

MSM1070 energy-converting hydrogenase B, subunit G, EhbG

MSM1071 energy-converting hydrogenase B, subunit F, EhbF

MSM1072 energy-converting hydrogenase B, subunit E, EhbE

MSM1073 energy-converting hydrogenase B, subunit D, EhbD

MSM1074 energy-converting hydrogenase B, subunit C, EhbC

MSM1075 energy-converting hydrogenase B, subunit B, EhbB

MSM1076 energy-converting hydrogenase B, subunit A, EhbA

MSM1077 putative permease (transport)

MSM1078 predicted bile acid/sodium symporter

MSM1079 predicted membrane-bound metal-dependent hydrolase, NCS2 family

MSM1080 predicted deacylase

MSM1081 transcriptional regulator (enhancer-binding protein), DNA2/NAM7 helicase family

MSM1082 hypothetical protein

MSM1083 conserved hypothetical membrane protein

MSM1084 argininosuccinate synthase, ArgG

MSM1085 aquaporin, MIP superfamily, AqpM

MSM1086 conserved hypothetical protein

MSM1087 NAD-dependent protein deacetylase, SIR2 family

MSM1088 hypothetical protein

MSM1089 hypothetical protein

MSM1090 sugar fermentation stimulation protein, SfsA

MSM1091 sugar kinase, YjeF-related protein family

MSM1092 formylmethanofuran:tertrahydromethanopterin formyltransferase, Ftr

MSM1093 putative transposase ND

MSM1094 conserved hypothetical integral membrane protein

MSM1095 Trk-type potassium transport system, membrane component, TrkH

MSM1096 Trk-type potassium transport system, NAD-binding component, TrkA

MSM1097 Zn-dependent hydrolase

MSM1098 archaeal holliday junction resolvase

MSM1099 biotin synthase related protein

MSM1100 conserved hypothetical protein

MSM1101 Asp-tRNA(Asn)/Glu-tRNA(Gln)amidotransferase, B subunit, GatB

MSM1102 IMP dehydrogenase related protein

MSM1103 phosphoribosyl-ATP pyrophosphohydrolase, HisE

MSM1104 acetyltransferase, GNAT family

MSM1105 NCAIR mutase related protein, PurE

MSM1106 hydrogenase maturation factor, HypF

MSM1107 predicted transcriptional regulator

MSM1108 molecular chaperone GrpE

MSM1109 molecular chaperone DnaJ

MSM1110 adhesin-like protein

MSM1111 adhesin-like protein

MSM1112 adhesin-like protein

MSM1113 adhesin-like protein

MSM1114 adhesin-like protein

MSM1115 putative transposase ND MSM1116 adhesin-like protein

MSM1117 cobalamin biosynthesis protein N, CobN

MSM1118 conserved hypothetical protein

MSM1119 conserved hypothetical protein

MSM1120 methionine aminopeptidase, Map

MSM1121 coenzyme F420-reducing hydrogenase, beta subunit, FrhB

MSM1122 coenzyme F420-reducing hydrogenase, gamma subunit, FrhG

MSM1123 coenzyme F420-reducing hydrogenase, delta subunit, FrhD

MSM1124 coenzyme F420-reducing hydrogenase, alpha subunit, FrhA

MSM1125 predicted endoglucanase (CobN-related)

MSM1126 predicted transcriptional regulator, ArsR family

MSM1127 cation transport ATPase, HAD family

MSM1128 hypothetical protein

MSM1129 conserved hypothetical protein

MSM1130 conserved hypothetical protein

MSM1131 conserved hypothetical protein

MSM1132 ribosome biogenesis protein Nop10

MSM1133 translation initiation factor alF-2, alpha subunit

MSM1134 ribosomal protein S27e

MSM1135 ribosomal protein L44e

MSM1136 conserved hypothetical protein

MSM1137 DNA polymerase sliding clamp subunit, PCNA family, Pcn

MSM1138 predicted glutamine amidotransferase, CobB/CobQ-like family

MSM1139 cell wall biosynthesis protein, MurD-like peptide ligase family

MSM1140 hypothetical protein

MSM1141 tryptophan synthase, alpha subunit, TrpA

MSM1142 tryptophan synthase, beta subunit, TrpB

MSM1143 indole-3-glycerol phosphate synthase, TrpC

MSM1144 anthranilate phosphoribosyltransferase, TrpD

MSM1145 anthranilate/para-aminobenzoate synthase component II, TrpG

MSM1146 anthranilate/para-aminobenzoate synthase component I, TrpE

MSM1147 hypothetical protein

MSM1148 predicted metal-dependent membrane protease

MSM1149 conserved hypothetical membrane protein

MSM1150 predicted transcriptional regulator

MSM1151 adenylosuccinate lyase, PurB

MSM1152 conserved hypothetical membrane protein

MSM1153 cation transport ATPase, HAD family

MSM1154 metal-dependent amidohydrolase

MSM1155 conserved hypothetical protein

MSM1156 tRNA pseudouridine synthase D, TruD

MSM1157 hypothetical protein

MSM1158 hydrogenase expression/formation protein, HypE

MSM1159 glutamine amidotransferase, HisH

MSM1160 nitrogenase molybdenum-iron protein, NifD

MSM1161 hypothetical protein

MSM1162 conserved hypothetical protein

MSM1163 hypothetical protein

MSM1164 predicted GTPase, HSR1-related family

MSM1165 predicted phosphohydrolase (metal-dependent)

MSM1166 conserved hypothetical membrane protein

MSM1167 cobalt precorrin-6Y C5, 15-methyltransferase, CbiE

MSM1168 putative adhesin-like protein

MSM1169 hypothetical protein

MSM1170 arsenite-transporting ATPase

MSM1171 ammonia-dependent NAD+synthetase, NadE

MSM1172 leucyl-tRNA synthetase, LeuS

MSM1173 tRNA(1-methyladenosine)methyltransferase

MSM1174 heat shock protein HtpX (Zn-dependent)

MSM1175 conserved hypothetical membrane protein

MSM1176 replication factor C, small subunit, RfcS

MSM1177 replication factor C, large subunit, RfcL

MSM1178 putative ATPase implicated in cell cycle control

MSM1179 shikimate 5-dehydrogenase, AroE

MSM1180 predicted metal-dependent membrane protease

MSM1181 histidyl-tRNA synthetase, HisS

MSM1182 phosphoribosyl-AMP cyclohydrolase, HisI

MSM1183 ATPase, PilT family

MSM1184 sugar phosphate isomerase/epimerase, AP endonuclease family 2

MSM1185 methylated-DNA-[protein]-cysteine S-methyltransferase

MSM1186 potassium transport system, membrane component, KefB

MSM1187 ERCC4-like helicase

MSM1188 adhesin-like protein

MSM1189 putative transposase ND MSM1190 cell wall biosynthesis protein, UDP-N-acetylmuramate-alanine ligase family

MSM1191 cell wall biosynthesis protein, MurD-like peptide ligase family

MSM1192 conserved hypothetical protein

MSM1193 single-stranded DNA-specific exonuclease, DHH family

MSM1194 ribosomal protein S15p

MSM1195 xanthosine triphosphate pyrophosphatase, Ham1 family

MSM1196 predicted archaeal ATPase, AAA+ superfamily

MSM1197 predicted ATPase, AAA+ superfamily

MSM1198 O-sialoglycoprotein endopeptidase

MSM1199 conserved hypothetical protein

MSM1200 phosphoribosyltransferase, CobT

MSM1201 undecaprenyl-diphosphatase, UppP

MSM1202 branched-chain-amino-acid aminotransferase, IIvE

MSM1203 Zn-dependent protease, peptidase M48 family

MSM1204 coenzyme F420-dependent methylenetetrahydromethanopterin dehydrogenase, Mtd

MSM1205 conserved hypothetical membrane protein

MSM1206 imidazoleglycerol-phosphate dehydrogenase, HisB

MSM1207 molybdate transport system regulatory protein

MSM1208 teichoic acid transporter

MSM1209 multimeric flavodoxin

MSM1210 efflux pump antibiotic resistance protein, MFS permease family

MSM1211 putative phosphoserine phosphatase

MSM1212 conserved hypothetical protein

MSM1213 3-hexulose 6-phosphate synthase/formaldehyde activating enzyme

MSM1214 threonyl-tRNA synthetase, ThrS

MSM1215 cobyrinic acid a,c-diamide synthase, CbiA

MSM1216 conserved hypothetical membrane protein

MSM1217 type II restriction endonuclease

MSM1218 predicted acid phosphatase (survival protein), SurE

MSM1219 hypothetical protein

MSM1220 small nucleolar ribonucleoprotein, Sm-like family

MSM1221 actin-like ATPase

MSM1222 ketol-acid reductoisomerase, IIvC

MSM1223 carbonic anhydrase

MSM1224 acetolactate synthase, small subunit (regulatory), IIvH

MSM1225 acetolactate synthase, large subunit (TPP-requiring), IIvB

MSM1226 ornithine carbamoyltransferase, ArgF

MSM1227 phosphoribosylamine-glycine ligase, PurD

MSM1228 Na+-driven multidrug efflux pump

MSM1229 Na+-driven multidrug efflux pump

MSM1230 transcriptional regulator, MarR family

MSM1231 arginyl-TRNA synthetase, ArgS

MSM1232 signal peptidase I

MSM1233 glutamate-1-semialdehyde 2,1-aminomutase, HemL

MSM1234 cobalt-precorrin-8X methylmutase, CbiC

MSM1235 predicted flavoprotein

MSM1236 aspartyl-tRNA synthetase, AspS

MSM1237 dihydroxy-acid dehydratase, IIvD

MSM1238 histidinol dehydrogenase, HisD

MSM1239 predicted DNA-binding protein

MSM1240 predicted AAA ATPase

MSM1241 chromosome partitioning ATPase

MSM1242 tryptophan synthase, beta subunit, TrpB

MSM1243 putative actin-like ATPase

MSM1244 predicted metal-dependent phosphoesterases, PHP family

MSM1245 archaeal DNA-binding protein, AlbA

MSM1246 isopropylmalate synthase, LeuA

MSM1247 serine/threonine protein kinase related protein (PQQ-binding)

MSM1248 multidrug ABC transporter, permease component

MSM1249 multidrug ABC transporter, ATPase component

MSM1250 predicted transcriptional regulator, PadR-like family

MSM1251 predicted sugar phosphate isomerase/epimerase, AP endonuclease family 2

MSM1252 cation transporting P-type ATPase, HAD family

MSM1253 glutamyl-tRNA (Gln) amidotransferase subunit A, GatA

MSM1254 cobyric acid synthase

MSM1255 hypothetical protein

MSM1256 3,4-dihydroxy-2-butanone 4-phosphate synthase, RibB

MSM1257 predicted transcriptional regulator of riboflavin/FAD biosynthetic operon

MSM1258 fumarate reductase/succinate dehydrogenase flavoprotein, Sdh

MSM1259 predicted metal-dependent hydrolase, TRZ/ATZ family

MSM1260 archaeal histone

MSM1261 ATP phosphoribosyltransferase, HisG

MSM1262 flavodoxin (protoporphyrinogen oxidase)

MSM1263 aspartate carbamoyltransferase, PyrB

MSM1264 cell division control protein 6, Cdc6

MSM1265 conserved hypothetical protein

MSM1266 cobalamin biosynthesis protein D, CobD

MSM1267 cobalamin biosynthesis protein G, CbiG

MSM1268 conserved hypothetical protein

MSM1269 putative Met repressor-like protein

MSM1270 fuculose-1-phosphate aldolase, class II aldolase/adducin family

MSM1271 archaeal DNA polymerase II, small subunit

MSM1272 conserved hypothetical protein

MSM1273 cobalt precorrin-3B C17-methyltransferase, CbiH

MSM1274 predicted potassium ion transport protein

MSM1275 mgtE-like divalent cation transporter

MSM1276 conserved hypothetical protein

MSM1277 conserved hypothetical membrane protein

MSM1278 predicted archaeal ATPase, AAA+ superfamily

MSM1279 predicted nucleic-acid-binding protein containing a Zn-ribbon

MSM1280 sirohydrochlorin cobaltochelatase, CbiX

MSM1281 sirohydrochlorin cobaltochelatase-related protein

MSM1282 putative adhesin-like protein

MSM1283 thiamine monphosphate kinase, ThiL

MSM1284 pyruvate formate-lyase activating enzyme, PflA

MSM1285 conserved hypothetical protein

MSM1286 3-octaaprenyl-4-hydroxybenzoate carboxy-lyase, UbiD

MSM1287 phosphoribosylaminoimidazole carboxylase (NCAIR muatse), PurE

MSM1288 conserved hypothetical membrane protein

MSM1289 GtrA-like surface polysaccharide biosynthesis protein, GtrA

MSM1290 glycosyltransferase (related to beta-glycosidases), GT2 family [CAZy]

MSM1291 conserved hypothetical membrane protein

MSM1292 transcriptional accessory protein, S1 RNA binding family, Tex

MSM1293 nitroreductase, NADH oxidase/flavin reductase family

MSM1294 glycosyltransferase, GT2 family

MSM1295 predicted DNA-binding protein

MSM1296 riboflavin synthase, beta subunit, RibH

MSM1297 glycosyltransferase, GT2 family

MSM1298 3-isopropylmalate dehydrogenase, LeuB

MSM1299 3-isopropylmalate dehydratase, small subunit, LeuD

MSM1300 3-isopropylmalate dehydratase, large subunit, LeuC

MSM1301 predicted Fe-S oxidoreductase

MSM1302 conserved hypothetical protein

MSM1303 UDP-N-acetyl-D-mannosaminuronate dehydrogenase

MSM1304 dTDP-4-dehydrorhamnose reductase, RfbD

MSM1305 adhesin-like protein

MSM1306 adhesin-like protein

MSM1307 dTDP-glucose pyrophosphorylase, RfbA

MSM1308 dTDP-4-dehydrorhamnose 3,5-epimerase

MSM1309 dTDP-D-glucose 4,6-dehydratase, RfbB

MSM1310 glycosyltransferase, GT2 family

MSM1311 glycosyltransferase, GT2 family

MSM1312 glycosyltransferase, GT2 family

MSM1313 distantly related to glycosyltransferases, GT4 family

MSM1314 hypothetical protein

MSM1315 predicted transcriptional regulator

MSM1316 glycosyltransferase, GT2 family

MSM1317 distantly related to glycosyltransferases, GT4 family

MSM1318 conserved hypothetical protein

MSM1319 conserved hypothetical protein

MSM1320 possible glycosyltransferase

MSM1321 predicted glycosyltransferase, GT2 family

MSM1322 distantly related to alpha-glycosyltransferases, GT4 family

MSM1323 glycosyltransferase, GT2 family

MSM1324 glycosyltransferase, GT2 family

MSM1325 predicted polysaccharide/polyol phosphate ABC transporter, permease component

MSM1326 polysaccharide/polyol phosphate ABC transporter, ATPase component

MSM1327 predicted CDP-glycerol:poly(glycerophosphate) glycerophosphotransferase

MSM1328 glycosyltransferase, GT2 family

MSM1329 predicted glycosyltransferase, GT2 family

MSM1330 predicted glycosyltransferase, GT2 family

MSM1331 bacterial sugar transferase, WcaJ

MSM1332 ssDNA-binding protein

MSM1333 DNA repair protein RadA, RadA

MSM1334 predicted permease

MSM1335 hypothetical protein

MSM1336 heterodisulfide reductase, subunit A, HdrA

MSM1337 glycine hydroxymethyltransferase, GlyA

MSM1338 archaeal flavoprotein

MSM1339 conserved hypothetical protein

MSM1340 archaeal S-adenosylmethionine synthetase, MetK

MSM1341 isoleucyl-tRNA synthetase, IIeS

MSM1342 phosphoribosylformylglycinamidine (FGAM) synthase, PurL

MSM1343 molybdenum cofactor biosynthesis protein, MoeA

MSM1344 predicted membrane-associated Zn-dependent protease

MSM1345 hypothetical protein

MSM1346 conserved hypothetical protein

MSM1347 hypothetical protein

MSM1348 rubrerythrin

MSM1349 F420H2-oxidase/flavoprotein, FprA

MSM1350 predicted transcriptional regulator, ArsR family

MSM1351 precorrin-2 C20-methyltransferase, CbiL

MSM1352 predicted ATP-dependent DNA helicase

MSM1353 putative topoisomerase IV, subunit A

MSM1354 DNA_directed RNA polymerase subunit M, RpoM

MSM1355 ADP-ribose pyrophosphatase, NUDIX hydrolase family

MSM1356 DNA-directed RNA polymerase, subunit L, RpoL

MSM1357 predicted RNA-binding protein

MSM1358 diphthamide synthase, subunit DPH2

MSM1359 adenine phosphoribosyltransferase, Apt

MSM1360 signal recognition particle GTPase SRP54

MSM1361 predicted pseudouridylate synthase

MSM1362 molybdenum cofactor biosynthesis protein C, MoaC

MSM1363 preprotein translocase, SecG subunit, SecG

MSM1364 imidazoleglycerol-phosphate synthase, HisF

MSM1365 3-methyladenine DNA glycosylase/8-oxoguanine DNA glycosylase

MSM1366 lactoylglutathione lyase, LgIU

MSM1367 peptidyl-prolyl cis-trans isomerase, PpiB

MSM1368 N-acetylornithine aminotransferase, ArgD

MSM1369 MutT-related protein, NUDIX family

MSM1370 conserved hypothetical membrane protein

MSM1371 diaminopimelate decarboxylase, LysA

MSM1372 diaminopimelate epimerase, DapF

MSM1373 methyltransferase, HemK

MSM1374 dimethyladenosine transferase, KsgA

MSM1375 predicted RNA-binding protein

MSM1376 DNA-directed RNA polymerase subunit F

MSM1377 ribosomal protein L21e

MSM1378 putative monooxygenase, ABM family

MSM1379 predicted NADP-dependent alcohol dehydrogenase

MSM1380 NADP-dependent alcohol dehydrogenase

MSM1381 putative NADP-dependent alcohol dehydrogenase

MSM1382 conserved hypothetical membrane protein

MSM1383 anaerobic ribonucleoside-triphosphate reductase, NrdD

MSM1384 archaeal DNA polymerase II, large subunit, PolC

MSM1385 predicted acyltransferase

MSM1386 cytosine deaminase

MSM1387 lysyl-tRNA synthetase (class I), LysS

MSM1388 thiamine biosynthesis protein, ThiC

MSM1389 sugar kinase, ribokinase/pfkB superfamily

MSM1390 transcriptional regulator, LysR family

MSM1391 predicted sugar phosphate isomerase involved in capsule formation, GutQ

MSM1392 formate dehydrogenase accessory protein FdhD, FdhD

MSM1393 iron(III) ABC transporter, substrate-binding component

MSM1394 iron(III) ABC transporter, permease component

MSM1395 iron(III) ABC transporter, ATPase component

MSM1396 tungsten formylmethanofuran dehydrogenase, subunit E, FwdE

MSM1397 adhesin-like protein

MSM1398 adhesin-like protein

MSM1399 adhesin-like protein

MSM1400 putative antimicrobial peptide ABC transporter, permease component

MSM1401 biopolymer transport protein

MSM1402 conserved hypothetical protein

MSM1403 formate/nitrite transporter, FdhC

MSM1404 formate dehydrogenase, alpha subunit, FdhA

MSM1405 formate dehydrogenase, beta subunit, FdhB

MSM1406 molybdopterin cofactor biosynthesis protein A, MoaA

MSM1407 molybdopterin-guanine dinucleotide biosynthesis protein B, MobB

MSM1408 tungsten formylmethanofuran dehydrogenase, subunit E, FwdE

MSM1409 tungsten formylmethanofuran dehydrogenase, subunit F, FwdF

MSM1410 tungsten formylmethanofuran dehydrogenase, subunit G, FwdG

MSM1411 tungsten formylmethanofuran dehydrogenase, subunit D, FwdD

MSM1412 tungsten formylmethanofuran dehydrogenase, subunit B, FwdB

MSM1413 tungsten formylmethanofuran dehydrogenase, subunit A, FwdA

MSM1414 tungsten formylmethanofuran dehydrogenase, subunit C, FwdC

MSM1415 conserved hypothetical protein

MSM1416 conserved hypothetical protein

MSM1417 conserved hypothetical protein

MSM1418 glutamine synthetase, GlnA

MSM1419 putative transposase ND MSM1420 helicase, UvrD/REP family

MSM1421 conserved hypothetical membrane protein

MSM1422 LemA protein

MSM1423 exopolyphosphatase, GppA

MSM1424 polyphosphate kinase, ppk

MSM1425 ribosomal protein S13p

MSM1426 ribosomal protein S4p

MSM1427 ribosomal protein S11p

MSM1428 DNA-directed RNA polymerase, subunit D, RpoD

MSM1429 ribosomal protein L18e

MSM1430 ribosomal protein L13p

MSM1431 ribosomal protein S9p

MSM1432 DNA-directed RNA polymerase, subunit N, RpoN

MSM1433 DNA-directed RNA polymerase, subunit K, RpoK

MSM1434 conserved hypothetical protein

MSM1435 enolase

MSM1436 ferredoxin

MSM1437 ribosomal protein S2p

MSM1438 predicted dioxygenase

MSM1439 mevalonate kinase

MSM1440 predicted archaeal kinase

MSM1441 isopentenyl-diphosphate delta-isomerase

MSM1442 predicted RNA hydrolase, metallo-beta-lactamase superfamily

MSM1443 bifunctional short chain isoprenyl diphosphate synthase, IdsA

MSM1444 conserved hypothetical membrane protein

MSM1445 predicted transcriptional regulator

MSM1446 predicted hydroxylamine reductase, Hcp

MSM1447 conserved hypothetical protein

MSM1448 SAM-dependent methyltransferase

MSM1449 putative O-linked GlcNAc transferase

MSM1450 predicted oxidoreductase, aldo/keto reductase family

MSM1451 best blast hit to TPR repeat protein (Mba); not predicted to be a carbohydrate active enzyme by CAZy

MSM1452 glutamyl-tRNA synthetase, GltX

MSM1453 hypothetical protein

MSM1454 predicted ATPase, AAA+family

MSM1455 aspartate/tyrosine/aromatic aminotransferase

MSM1456 conserved hypothetical protein

MSM1457 hypothetical protein

MSM1458 hypothetical protein

MSM1459 multidrug efflux permease, AraJ

MSM1460 energy-converting hydrogenase B, subunit K, EhbK

MSM1461 methyl viologen-reducing hydrogenase, delta subunit, MvhD

MSM1462 formate dehydrogenase, beta subunit, FdhB

MSM1463 formate dehydrogenase, alpha subunit, FdhA

MSM1464 FlpE-related protein

MSM1465 multidrug efflux permease, AraJ

MSM1466 hypothetical protein

MSM1467 hypothetical protein

MSM1468 adenylosuccinate synthetase, PurA

MSM1469 nitrate/sulfonate/bicarbonate ABC transporter, substrate-binding component, TauA

MSM1470 hypothetical protein

MSM1471 acyl-CoA synthetase

MSM1472 conserved hypothetical protein

MSM1473 metal-dependent hydrolase, beta-lactamase superfamily

MSM1474 chorismate synthase, AroC

MSM1475 predicted endonuclease III-related protein

MSM1476 porphobilinogen synthase, HemB

MSM1477 ATP:dephospho-CoA triphosphoribosyl transferase

MSM1478 phenylalanyl-tRNA synthetase, PheS

MSM1479 exodeoxyribonuclease, XthA

MSM1480 predicted hydrolase, HAD superfamily

MSM1481 DNA-directed DNA polymerase, family B, PolB

MSM1482 hypothetical protein

MSM1483 multidrug ABC transporter, ATPase component

MSM1484 multidrug ABC transporter, permease component

MSM1485 putative adhesin-like protein

MSM1486 ribosomal protein S8e

MSM1487 conserved hypothetical protein

MSM1488 cobalt ABC transporter, permaease component, CbiM

MSM1489 protein related to formylmethanofuran dehydrogenase subunit E, metalbinding

MSM1490 conserved hypothetical protein

MSM1491 protein related to formylmethanofuran dehydrogenase subunit E, metalbinding

MSM1492 hydrogenase maturation factor, HypE

MSM1493 conserved hypothetical membrane protein, RDD family

MSM1494 hypothetical protein

MSM1495 nuclease, Staphylococcus nuclease-like family

MSM1496 conserved hypothetical protein

MSM1497 predicted coenzyme PQQ synthesis protein

MSM1498 helicase

MSM1499 predicted transcriptional regulator

MSM1500 ssDNA exonuclease, RecJ

MSM1501 signal recognition particle, subunit SRP19

MSM1502 UDP-galactopyranose mutase

MSM1503 glycosyltransferase, GT2 family

MSM1504 uroporphyrinogen III synthase, HemD

MSM1505 hypothetical protein

MSM1506 hypothetical protein

MSM1507 glycosyltransferase, GT2 family

MSM1508 hypothetical protein

MSM1509 hypothetical protein

MSM1510 putative SAM-dependent methyltransferase

MSM1511 hypothetical protein

MSM1512 lipopolysaccharide cholinephosphotransferase, LicD family

MSM1513 aspartate aminotransferase

MSM1514 glycerol-3-phosphate cytidyltransferase, TagD

MSM1515 lipopolysaccharide cholinephosphotransferase, LicD family

MSM1516 histidinol-phosphate aminotransferase, HisC

MSM1517 ornithine cyclodeaminase

MSM1518 IS element ISM1 (ICSNY family)

MSM1519 IS element ISM1 (ICSNY family)

MSM1520 IS element ISM1 (ICSNY family)

MSM1521 hypothetical protein

MSM1522 hypothetical protein

MSM1523 transposase

MSM1524 conserved hypothetical protein

MSM1525 conserved hypothetical protein

MSM1526 conserved hypothetical membrane protein

MSM1527 predicted ATPase, AAA+ superfamily

MSM1528 predicted transcriptional regulator, HTH XRE-like family

MSM1529 putative Zn peptidase

MSM1530 putative nucleic acid-binding protein

MSM1531 Na+-dependent transporter, SNF family

MSM1532 Na+-dependent transporter, SNF family

MSM1533 adhesin-like protein

MSM1534 adhesin-like protein

MSM1535 predicted dTDP-D-glucose 4,6-dehydratase

MSM1536 pleiotropic regulatory protein DegT (PLP-dependent)

MSM1537 predicted acylneuraminate cytidylyltransferase, NeuS

MSM1538 CMP-sialic acid synthetase, NeuA

MSM1539 sialic acid synthase, NeuB

MSM1540 glycerol-3-phosphate dehydrogenase (NAD)

MSM1541 hypothetical protein

MSM1542 4-diphosphocytidyl-2-methyl-D-erithritol synthase, IspD

MSM1543 hypothetical protein

MSM1544 lipopolysaccharide cholinephosphotransferase

MSM1545 glycosyltransferase, GT2 family

MSM1546 hypothetical protein

MSM1547 phosphoribosylaminoimidazole-succinocarboxamide (SAICAR) synthase, PurC

MSM1548 phosphoribosylformylglycinamidine (FGAM) synthase, PurS

MSM1549 phosphoribosylformylglycinamidine (FGAM) synthase, PurQ

MSM1550 uroporphyrin-III C-methyltransferase, CobA

MSM1551 glucosamine--fructose-6-phosphate aminotransferase, GlmS

MSM1552 hypothetical protein

MSM1553 hypothetical protein

MSM1554 putative adhesin-like protein

MSM1555 SAM-dependent methyltransferase

MSM1556 conserved hypothetical protein

MSM1557 queuine/archaeosine tRNA-ribosyltransferase

MSM1558 SAM-dependent methyltransferase, UbiE family

MSM1559 polysaccharide biosynthesis protein, MviN-like family

MSM1560 polysaccharide biosynthesis protein, MviN-like family

MSM1561 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase

MSM1562 acetyl-CoA acyltransferase, SCP-type thiolase family

MSM1563 hypothetical protein

MSM1564 predicted SAM-dependent methyltransferase

MSM1565 cobyric acid synthase, CobQ

MSM1566 putative transposase ND

MSM1567 adhesin-like protein

MSM1568 putative transcription regulator

MSM1569 ATP-dependent protease La, LonB

MSM1570 cell wall biosynthesis protein, MurD-like peptide ligase family

MSM1571 hypothetical protein

MSM1572 ADP-ribosylglycohydrolase

MSM1573 N-acetyltransferase, GNAT family

MSM1574 nitroreductase, NfnB

MSM1575 hypothetical protein

MSM1576 hypothetical protein

MSM1577 ribose-phosphate pyrophosphokinase, PrsA

MSM1578 hypothetical protein

MSM1579 excinuclease ABC, subunit B, UvrB

MSM1580 hypothetical protein

MSM1581 excinuclease ABC, subunit A, UvrA

MSM1582 conserved hypothetical membrane protein

MSM1583 archaea-specific helicase

MSM1584 predicted excinuclease ABC, C subunit, UvrC

MSM1585 adhesin-like protein

MSM1586 adhesin-like protein

MSM1587 adhesin-like protein

MSM1588 transposase

MSM1589 transposase, RNase-H-like family ND

MSM1590 adhesin-like protein

MSM1591 conserved hypothetical protein

MSM1592 polysaccharide/polyol phosphate ABC transporter, ATPase component

MSM1593 polysaccharide/polyol phosphate ABC transporter, permease component

MSM1594 glycosyltransferase/CDP-glycerol:poly(glycerophosphate) glycerophosphotransferase, GT2 family

MSM1595 SAM-dependent methyltransferase, FkbM family

MSM1596 putative transposase ND MSM1597 hypothetical protein

MSM1598 SAM-dependent methyltransferase

MSM1599 SAM-dependent methyltransferase

MSM1600 putative acetyltransferase, trimeric LpxA-like family

MSM1601 conserved hypothetical protein

MSM1602 glycosyltransferase/CDP-glycerol:poly(glycerophosphate) glycerophosphotransferase, GT2 family

MSM1603 conserved hypothetical protein

MSM1604 UDP-glucose pyrophosphorylase, GalU

MSM1605 hypothetical protein

MSM1606 arylsulfatase regulator, AsIB

MSM1607 conserved hypothetical protein

MSM1608 predicted oxidoreductase, aldo/keto reductase family

MSM1609 molybdate ABC transporter, substrate-binding component, ModA

MSM1610 molybdate ABC transporter, permease component, ModC

MSM1611 molybdate ABC transporter, ATPase component, ModB

MSM1612 predicted UDP-glucose 6-dehydrogenase

MSM1613 predicted UDP-glucose/GDP-mannose dehydrogenase

MSM1614 predicted transcriptional regulator

MSM1615 deoxyhypusine synthase, Dys

MSM1616 conserved hypothetical protein

MSM1617 orotidine-5′-phosphate decarboxylase, PyrF

MSM1618 cobalamin biosynthesis protein M, CbiM

MSM1619 cobalt ABC transporter, substrate-binding component, CbiN

MSM1620 cobalt ABC transporter, permease component, CbiQ

MSM1621 cobalt ABC transporter, ATPase component, CbiO

MSM1622 archaeal riboflavin synthase, RibC

MSM1623 glycosyltransferase/dolichyl-phosphate mannose synthase, GT2 family

MSM1624 conserved hypothetical protein

MSM1625 thiol:fumarate reductase, subunit B, TfrB

MSM1626 predicted fumarate reductase

MSM1627 glycosyltransferase, GT2 family

MSM1628 conserved hypothetical protein, aldolase family

MSM1629 IMP dehydrogenase/GMP reductase, GuaB

MSM1630 ribosomal protein L37Ae

MSM1631 predicted DNA-directed RNA polymerase II, subunit RPC10

MSM1632 predicted brix-domain ribosomal biogenesis protein

MSM1633 conserved hypothetical protein

MSM1634 prefoldin, beta subunit

MSM1635 conserved hypothetical protein

MSM1636 ProFAR isomerase-related protein

MSM1637 conserved hypothetical membrane protein

MSM1638 conserved hypothetical membrane protein

MSM1639 heavy metal cation (Co/Zn/Cd) efflux system protein, CzcD family

MSM1640 DNA intergrase/recombinase, phage integrase family

MSM1641 hypothetical protein

MSM1642 conserved hypothetical protein

MSM1643 hypothetical protein

MSM1644 hypothetical protein

MSM1645 virulence protein

MSM1646 putative ATPase (AAA+ superfamily)

MSM1647 hypothetical protein

MSM1648 hypothetical protein

MSM1649 hypothetical protein

MSM1650 hypothetical protein

MSM1651 hypothetical protein

MSM1652 hypothetical protein

MSM1653 hypothetical protein

MSM1654 putative Gp40-related protein, ERF family single-strand annealing protein

MSM1655 hypothetical protein

MSM1656 hypothetical protein

MSM1657 conserved hypothetical protein

MSM1658 hypothetical protein

MSM1659 hypothetical protein

MSM1660 hypothetical protein

MSM1661 hypothetical protein

MSM1662 hypothetical protein

MSM1663 hypothetical protein

MSM1664 hypothetical protein

MSM1665 hypothetical protein

MSM1666 hypothetical protein

MSM1667 hypothetical protein

MSM1668 hypothetical protein

MSM1669 hypothetical protein

MSM1670 hypothetical protein

MSM1671 large terminase subunit

MSM1672 bacteriophage capsid portal protein

MSM1673 conserved hypothetical protein

MSM1674 hypothetical protein

MSM1675 putative structural protein

MSM1676 hypothetical protein

MSM1677 putative major capsid protein gp5

MSM1678 hypothetical protein

MSM1679 hypothetical protein

MSM1680 hypothetical protein

MSM1681 hypothetical protein

MSM1682 hypothetical protein

MSM1683 hypothetical protein

MSM1684 phage-related minor tail protein

MSM1685 hypothetical protein

MSM1686 hypothetical protein

MSM1687 conserved hypothetical protein

MSM1688 hypothetical protein

MSM1689 putative collagen-like protein B

MSM1690 hypothetical protein

MSM1691 putative pseudomurein endoisopeptidase, PeiW

MSM1692 hypothetical protein

MSM1693 predicted ribokinase, PfkB family

MSM1694 predicted helicase

MSM1695 excinuclease ABC, subunit C, UvrC

MSM1696 conserved hypothetical protein

MSM1697 hypothetical protein

MSM1698 methyl coenzyme M reductase system, component A2-like

MSM1699 predicted universal stress protein, UspA

MSM1700 predicted ferredoxin

MSM1701 predicted FAD-dependent dehydrogenase, geranylgeranyl reductase family

MSM1702 UDP-glucose 4-epimerase

MSM1703 conserved hypothetical protein

MSM1704 glutamine phosphoribosylpyrophosphate amidotransferase, PurF

MSM1705 predicted collagenase, peptidase family U32

MSM1706 CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase

MSM1707 nitrogenase NifH subunit, NifH

MSM1708 hypothetical protein

MSM1709 adhesin-like protein

MSM1710 seryl-tRNA synthetase, SerS

MSM1711 conserved hypothetical protein

MSM1712 predicted ferritin

MSM1713 predicted regulatory protein, amino acid-binding ACT domain family

MSM1714 coenzyme F390 synthetase

MSM1715 magnesium chelatase subunit

MSM1716 adhesin-like protein

MSM1717 predicted transporter

MSM1718 predicted biopolymer transport protein

MSM1719 conserved hypothetical protein

MSM1720 DNA-directed RNA polymerase, subunit M, RpoM

MSM1721 voltage gated chloride channel protein/cation transporter, TrkA family

MSM1722 nitroreductase

MSM1723 N5,N10-methenyl-tetrahydromethanopterin cyclohydrolase, Mch

MSM1724 conserved hypothetical membrane protein

MSM1725 conserved hypothetical membrane protein

MSM1726 conserved hypothetical membrane protein

MSM1727 multimeric flavodoxin

MSM1728 hypothetical protein

MSM1729 conserved hypothetical protein

MSM1730 conserved hypothetical membrane protein

MSM1731 short chain dehydrogenase/reductase

MSM1732 conserved hypothetical protein

MSM1733 rubrerythrin

MSM1734 predicted thymidylate synthase, ThyA

MSM1735 adhesin-like protein

MSM1736 permease, xanthine/uracil/vitamin C permease family

MSM1737 putative transcription regulator

MSM1738 putative adhesin-like protein

MSM1739 conserved hypothetical membrane protein

MSM1740 O-linked GlcNAc transferase

MSM1741 conserved hypothetical protein

MSM1742 predicted integrase, phage integrase-like family

MSM1743 predicted type II restriction enzyme, methylase subunit

MSM1744 predicted type II restriction enzyme, methylase subunit

MSM1745 predicted type II restriction enzyme, methylase subunit

MSM1746 predicted type II restriction enzyme, methylase subunit

MSM1747 predicted type II restriction enzyme, methylase subunit

MSM1748 predicted type II restriction enzyme, methylase subunit

MSM1749 conserved hypothetical protein

MSM1750 conserved hypothetical protein

MSM1751 conserved hypothetical protein

MSM1752 predicted restriction endonuclease

MSM1753 conserved hypothetical protein

MSM1754 predicted ATP-dependent protease La, Lon

MSM1755 purine/pyrimidine phosphoribosyl transferase

MSM1756 Smf protein

MSM1757 hypothetical protein

MSM1758 hypothetical protein

MSM1759 hypothetical protein

MSM1760 hypothetical protein

MSM1761 predicted ATPase involved in DNA repair

MSM1762 hypothetical protein

MSM1763 predicted DNA-directed RNA polymerase, subunit M, RpoM

MSM1764 conserved hypothetical protein

MSM1765 conserved hypothetical protein

MSM1766 O-linked GlcNAc transferase

MSM1767 hypothetical protein

MSM1768 hypothetical protein

MSM1769 conserved hypothetical membrane protein

MSM1770 conserved hypothetical membrane protein

MSM1771 DNA helicase, UvrD/REP helicase family

MSM1772 conserved hypothetical protein

MSM1773 conserved hypothetical protein

MSM1774 hypothetical protein

MSM1775 putative topoisomerase IV, subunit A

MSM1776 TPR repeat protein

MSM1777 putative transcription regulator

MSM1778 conserved hypothetical protein

MSM1779 conserved hypothetical protein

MSM1780 conserved hypothetical membrane protein

MSM1781 conserved hypothetical protein

MSM1782 hypothetical protein

MSM1783 hypothetical protein

MSM1784 hypothetical protein

MSM1785 conserved hypothetical protein

MSM1786 O-linked GlcNAc transferase

MSM1787 O-linked GlcNAc transferase

MSM1788 O-linked GlcNAc transferase

MSM1789 predicted ATPase, AAA+ superfamily

MSM1790 predicted ATPase, AAA+ superfamily

MSM1791 conserved hypothetical protein

MSM1792 nicotinate phosphoribosyltransferase

MSM1793 conserved hypothetical protein

MSM1794 predicted tubulin-like protein

MSM1795 predicted ATPase, AAA+ superfamily

¹GeneChip-based genotyping of M. smithii strains done in duplicate; ‘present’or ‘absent’calls were determined using a perfect match/mismatch (PM/MM) model in dChip (see Methods). Note that the term ‘absent’is based on different criteria than those used for the human microbiome dataset (see footnote 2). ²Metagenomic datasets from the microbiomes of two healthy lean adults (Gill et al., 2006) were tested for identity to M. smithii PS ORFs; ORFs with reads that matched with >95% identity are called ‘present’, 80-95% identity are called ‘divergent’, and <80% identity are called ‘absent’. ^(ii)Probeset for M. smithii gene not represented on GeneChip.

TABLE 3 Transcriptional regulators identified in the M. smithii PS proteome ORF COG ANNOTATION MSM0026 COG1396 predicted transcriptional regulator (possible epoxidase activity) MSM0094 predicted transcription regulator (TetR family) MSM0155 COG2061 predicted allosteric regulator of homoserine dehydrogenase MSM0218 COG1321 iron dependent transcriptional regulator (Fe2+-binding) MSM0233 COG0347 nitrogen regulatory protein P-II, GlnK MSM0255 putative transcription regulator (winged helix DNA-binding domain) MSM0269 COG2522 predicted transcriptional regulator (lambda repressor-like) MSM0329 COG1396 DNA binding protein, xenobiotic response element family MSM0354 COG1222 ATP-dependent 26S proteasome regulatory subunit, RPT1 MSM0364 COG0864 transcriptional regulator (nickel-responsive), NikR MSM0383 COG1409 predicted phosphohydrolase, calcineurin-like superfamily MSM0388 COG4747 amino acid regulator (ACT domain) MSM0404 COG4742 predicted transcriptional regulator MSM0413 COG1846 transcriptional regulator, MarR family MSM0417 COG4068 predicted transmembrane protein with a zinc ribbon DNA-binding domain MSM0452 predicted DNA-binding protein MSM0453 COG1395 predicted transcriptional regulator MSM0540 COG2865 predicted transcriptional regulator MSM0564 COG0704 phosphate uptake regulator, PhoU MSM0569 COG0704 phosphate transport system regulator related protein, PhoU MSM0600 COG1846 transcriptional regulator, MarR family MSM0635 COG2150 predicted regulator of amino acid metabolism MSM0650 COG1309 transcriptional regulator, TetR/AcrR family MSM0766 COG0340 biotin-[acetyl-CoA-carboxylase] ligase/biotin operon regulator bifunctional protein, BirA MSM0775 COG2207 transcriptional regulator, AraC family MSM0817 COG4742 predicted transcriptional regulator MSM0818 COG4742 predicted transcriptional regulator MSM0819 COG0640 putative transcription regulator, ArsR family (winged helix DNA-binding domain) MSM0851 COG1548 predicted transcriptional regulator MSM0862 COG1781 aspartate carbamoyltransferase regulatory chain, PyrI MSM0864 COG1733 predicted transcriptional regulator MSM0936 COG0603 transcription regulator-related ATPase, ExsB MSM0966 COG1223 predicted 26S protease regulatory subunit (ATP-dependent), AAA+ family ATPase MSM1030 COG0399 predicted pyridoxal phosphate-dependent enzyme MSM1032 COG1522 transcriptional regulator, Lrp family MSM1081 COG1112 transcriptional regulator, DNA2/NAM7 helicase family MSM1090 COG1489 sugar fermentation stimulation protein, SfsA MSM1106 COG0068 hydrogenase maturation factor, HypF MSM1107 COG1777 predicted transcriptional regulator MSM1126 COG0640 predicted transcriptional regulator, ArsR family (arsenic) MSM1150 COG1476 predicted transcriptional regulator MSM1207 COG2005 molybdate transport system regulatory protein MSM1224 COG0440 acetolactate synthase, small subunit (regulatory), IlvH MSM1230 COG1846 transcriptional regulator, MarR family MSM1250 COG1695 predicted transcriptional regulator, PadR-like family MSM1257 COG1339 predicted transcriptional regulator of riboflavin/FAD biosynthetic operon MSM1292 COG2183 transcriptional accessory protein, S1 RNA binding family, Tex MSM1315 COG2865 predicted transcriptional regulator MSM1350 COG0640 predicted transcriptional regulator, ArsR family MSM1390 COG0583 transcriptional regulator, LysR family MSM1445 COG1378 predicted transcriptional regulator MSM1499 COG1497 predicted transcriptional regulator MSM1528 COG1396 predicted transcriptional regulator, HTH XRE-like family (xenobiotic) MSM1536 COG0399 pleiotropic regulatory protein DegT (PLP-dependent) MSM1568 putative transcription regulator MSM1606 COG0641 arylsulfatase regulator, AslB MSM1614 COG2524 predicted transcriptional regulator MSM1713 COG4747 predicted regulatory protein, amino acid-binding ACT domain family MSM1737 putative transcription regulator MSM1777 putative transcription regulator

TABLE 4 Machinery for genome evolution in M. smithii strain PS ORF ANNOTATION Restriction MSM0157 predicted type I restriction-modification enzyme, subunit S Modification MSM0158 type I restriction-modification system methylase, subunit S System MSM1187 predicted type III restriction enzyme Subunits MSM1217 type II restriction endonuclease MSM1743 predicted type II restriction enzyme, methylase subunit MSM1744 predicted type II restriction enzyme, methylase subunit MSM1745 predicted type II restriction enzyme, methylase subunit MSM1746 predicted type II restriction enzyme, methylase subunit MSM1747 predicted type II restriction enzyme, methylase subunit MSM1748 predicted type II restriction enzyme, methylase subunit MSM1752 predicted restriction endonuclease Recombination/ MSM0023 uncharacterized protein predicted to be involved in DNA repair Repair MSM0097 Mg-dependent DNase, TatD MSM0120 purine NTPase involved in DNA repair, Rad50 MSM0121 DNA repair exonuclease (SbcD/Mre11-family), Rad32 MSM0163 conserved hypothetical proetin predicted to be involved in DNA repair MSM0164 conserved hypothetical protein predicted to be involved in DNA repair MSM0167 conserved hypothetical protein predicted to be involved in DNA repair MSM0168 conserved hypothetical protein predicted to be involved in DNA repair MSM0170 conserved hypothetical protein predicted to be involved in DNA repair MSM0405 predicted metal-dependent DNase, TatD-related family MSM0416 Mg-dependent DNase, TatD-related MSM0524 DNA mismatch repair ATPase, MutS MSM0543 DNA repair photolyase, SplB MSM0611 DNA repair protein, RadB MSM0693 ATPase involved in DNA repair, SbcC MSM0695 DNA repair helicase MSM0725 DNA repair flap structure-specific 5′-3′ endonuclease MSM1193 single-stranded DNA-specific exonuclease, DHH family MSM1333 DNA repair protein RadA, RadA MSM1500 ssDNA exonuclease, RecJ MSM1640 DNA intergrase/recombinase, phage integrase family MSM1761 predicted ATPase involved in DNA repair IS elements MSM0527 IS element ISM1 (ICSNY family) MSM0528 IS element ISM1 (ICSNY family) MSM0532 IS element ISM1 (ICSNY family) MSM0533 IS element ISM1 (ICSNY family) MSM0534 IS element ISM1 (ICSNY family) MSM1518 IS element ISM1 (ICSNY family) MSM1519 IS element ISM1 (ICSNY family) MSM1520 IS element ISM1 (ICSNY family) Transposases MSM0008 putative transposase or remnants of MSM0087 putative transposase transposases MSM0110 predicted transposase MSM0230 putative transposase MSM0256 putative transposase MSM0342 putative transposase MSM0396 putative transposase MSM0458 transposase, homeodomain-like superfamily MSM0460 predicted transposase MSM0601 putative transposase MSM0629 putative transposase MSM0730 putative transposase MSM0871 putative transposase MSM1093 putative transposase MSM1115 putative transposase MSM1189 putative transposase MSM1419 putative transposase MSM1523 transposase MSM1566 putative transposase MSM1588 predicted transposase MSM1589 predicted transposase, RNaseH-like family MSM1596 putative transposase

TABLE 5 Publicly available finished genome sequences for members of Archaea GenBank Habitat of Accession Group Strain Designation Abbr. Temp. Origin Number Human Gut Methanobrevibacter smithii PS (ATCC 35021) Msm Mesophilic Host-associated CP000678 Methanogens Methanosphaera stadtmanae DSM 3091 Msp Mesophilic Host-associated CP000102 Non-Gut Methanothermobacter thermautotrophicus Mth Thermophilic Specialized AE000666 Delta H Methanogens Methanocaldococcus jannaschii DSM 2661 Mja Hyperthermophilic Aquatic L77117 Methanococcoides burtonii DSM 6242 Mbu Mesophilic Aquatic CP000300 Methanococcus maripaludis S2 Mmr Mesophilic Aquatic BX950229 Methanopyrus kandleri AV19 Mka Hyperthermophilic Specialized AE009439 Methanosarcina acetivorans C2A Mac Mesophilic Aquatic AE010299 Methanosarcina barkeri str. Fusaro Mba Mesophilic Multiple CP000099 Methanosarcina mazei Go1 Mma Mesophilic Multiple AE008384 Methanospirillum hungatei JF-1 Mhu Mesophilic Multiple CP000254 Other Archaea Aeropyrum pernix K1 Apx Hyperthermophilic Specialized BA000002 Archaeoglobus fulgidus DSM 4304 Afu Hyperthermophilic Aquatic AE000782 Haloarcula marismortui ATCC 43049 Hma Mesophilic Aquatic AY596297 Halobacterium sp. NRC-1 Hal Mesophilic Specialized AE004437 Nanoarchaeum equitans Kin4-M Neq Hyperthermophilic Host-associated AE017199 Natronomonas pharaonis DSM 2160 Nph Mesophilic Aquatic CR936257 Picrophilus torridus DSM 9790 Pto Thermophilic Specialized AE017261 Pyrobaculum aerophilum str. IM2 Pae Hyperthermophilic Aquatic AE009441 Pyrococcus abyssi GE5 Pab Hyperthermophilic Aquatic AL096836 Pyrococcus furiosus DSM 3638 Pfu Hyperthermophilic Aquatic AE009950 Pyrococcus horikoshii OT3 Pho Hyperthermophilic Aquatic BA000001 Sulfolobus acidocaldarius DSM 639 Sac Thermophilic Specialized CP000077 Sulfolobus solfataricus P2 Sso Hyperthermophilic Specialized AE006641 Sulfolobus tokodaii str. 7 Sto Hyperthermophilic Specialized BA000023 Thermococcus kodakarensis KOD1 Tko Hyperthermophilic Specialized AP006878 Thermoplasma acidophilum DSM 1728 Tac Thermophilic Specialized AL139299 Thermoplasma volcanium GSS1 Tvo Thermophilic Specialized BA000011

TABLE 6 Representation of enriched gene ontology (GO) categories in the M. smithil PS and M. stadtmanae proteomes compared to the proteomes of all sequenced methanogenic archaea and all archaea

Abbreviations: ‘non-gut-associated methanogens’ (Meth) or ‘all Archaea’ (Arch) [see SI Table 5]; No., number of genes associated with gene ontology (GO) term.

TABLE 7 M. smithii strain PS genes in the significantly enriched GO categories listed in Table 6

TABLE 8 M. smithii proteins with homologs in other sequenced Methanobacteriales Methanothermobacter M. smithii Methanosphaera stadmanae thermoautotrophicus ORF ORF ANNOTATION E-value ORF ANNOTATION E-value MSM0001 Msp_0220 predicted glycosyltransferase 4.2E−08 NONE MSM0002 Msp_1355 predicted site-specific 2.0E−08 MTH_893 integrase-recombinase 8.1E−16 recombinase/integrase protein MSM0003 Msp_0548 hypothetical membrane-spanning 6.8E−09 NONE protein MSM0004 Msp_0803 conserved hypothetical protein 2.3E−24 NONE MSM0005 Msp_0783 hypothetical membrane-spanning 3.7E−05 MTH_1439 unknown 6.2E−04 protein MSM0006 Msp_0725 hypothetical protein 1.3E−05 MTH_1277 unknown 3.3E−05 MSM0007 NONE MTH_675 unknown 1.1E−34 MSM0008 Msp_0017 conserved hypothetical protein 1.7E−28 NONE MSM0009 NONE MTH_675 unknown 8.1E−34 MSM0010 Msp_0813 conserved hypothetical protein 1.5E−36 MTH_676 unknown 1.7E−40 MSM0011 NONE NONE MSM0012 Msp_0317 hypothetical protein 3.3E−04 NONE MSM0013 NONE NONE MSM0014 NONE MTH_1289 heat shock protein GrpE 2.6E−04 MSM0015 NONE NONE MSM0016 NONE NONE MSM0017 NONE NONE MSM0018 NONE NONE MSM0019 NONE NONE MSM0020 Msp_1323 conserved hypothetical protein 1.4E−05 MTH_83 O-linked GlcNAc 3.3E−07 transferase MSM0021 Msp_0047 predicted short chain 3.7E−40 NONE dehydrogenase MSM0022 NONE NONE MSM0023 Msp_0424 conserved hypothetical protein 1.6E−25 MTH_1084 conserved protein 4.4E−18 MSM0024 NONE NONE MSM0025 Msp_0447 predicted acyl-CoA synthetase 3.7E−49 MTH_657 long-chain-fatty-acid-CoA 8.7E−227 ligase MSM0026 Msp_0265 conserved hypothetical protein 2.0E−16 MTH_659 epoxidase 4.1E−62 MSM0027 Msp_0667 putative glutamate synthase, 7.9E−70 NONE glutamate synthase 4.6E−79 subunit 2 with ferredoxin domain (NADPH), alpha subunit MSM0028 Msp_0602 conserved hypothetical protein 1.9E−13 MTH_1876 conserved protein 1.7E−04 MSM0029 NONE NONE MSM0030 Msp_0741 conserved hypothetical 1.8E−72 MTH_1812 conserved protein 1.6E−44 membrane-spanning protein MSM0031 Msp_1465 member of asn/thr-rich large 2.9E−23 MTH_716 cell surface glycoprotein 3.7E−04 protein family (s-layer protein) MSM0032 NONE NONE MSM0033 Msp_0966 putative 2-dehydropantoate 2- 6.8E−112 NONE reductase MSM0034 Msp_0725 hypothetical protein 7.9E−06 NONE MSM0035 NONE NONE MSM0036 NONE NONE MSM0037 NONE NONE MSM0038 NONE NONE MSM0039 NONE NONE MSM0040 Msp_1274 conserved hypothetical protein 5.5E−05 NONE MSM0041 NONE NONE MSM0042 NONE NONE MSM0043 Msp_0737 putative peptide methionine 1.6E−32 MTH_535 peptide methionine 5.3E−16 sulfoxide reductase MsrA/MsrB sulfoxide reductase MSM0044 Msp_0510 putative aspartate 2.0E−15 MTH_1894 aspartate 3.9E−13 aminotransferase aminotransferase homolog MSM0045 Msp_0283 predicted ATPase 3.9E−93 MTH_1176 nucleotide-binding protein 1.4E−70 (putative ATPase) MSM0046 Msp_1460 predicted NAD(FAD)-dependent 8.4E−114 MTH_1354 NADH oxidase 2.0E−149 dehydrogenase MSM0047 NONE NONE MSM0048 Msp_0701 hypothetical protein 4.0E−20 NONE MSM0049 Msp_0665 F420H2:NADP oxidoreductase 3.1E−75 MTH_248 conserved protein 9.4E−56 MSM0050 Msp_1172 conserved hypothetical protein 1.7E−21 NONE MSM0051 Msp_1399 member of asn/thr-rich large 4.0E−33 MTH_716 cell surface glycoprotein 3.9E−11 protein family (s-layer protein) MSM0052 Msp_0145 member of asn/thr-rich large 1.4E−53 MTH_716 cell surface glycoprotein 1.8E−11 protein family (s-layer protein) MSM0053 Msp_0086 putative tRNA 5.0E−100 MTH_584 tRNA 2.5E−110 nucleotidyltransferase nucleotidyltransferase MSM0054 Msp_0089 predicted 2′-5′ RNA ligase 7.2E−37 MTH_583 conserved protein 9.1E−42 MSM0055 Msp_0090 predicted 3-dehydroquinate 3.5E−108 MTH_580 conserved protein 3.3E−124 synthase MSM0056 Msp_0091 predicted fructose-bisphosphate 1.5E−100 MTH_579 conserved protein 2.9E−100 aldolase MSM0057 Msp_0762 member of asn/thr-rich large 1.7E−13 MTH_716 cell surface glycoprotein 8.2E−07 protein family (s-layer protein) MSM0058 Msp_0128 predicted helicase 8.6E−23 MTH_472 DNA helicase II 1.2E−90 MSM0059 Msp_0092 conserved hypothetical protein 9.4E−35 MTH_578 unknown 2.1E−49 MSM0060 Msp_1187 predicted archaeal kinase 8.2E−52 MTH_577 conserved protein 2.1E−49 MSM0061 Msp_0757 predicted ATPase 7.5E−97 NONE MSM0062 Msp_0554 hypothetical protein 2.2E−08 MTH_847 unknown 6.9E−08 MSM0063 Msp_1186 predicted hydrolase 1.3E−67 MTH_576 conserved protein 7.0E−51 MSM0064 Msp_0099 conserved hypothetical protein 4.6E−10 MTH_812 conserved protein 1.5E−09 MSM0065 Msp_1185 putative 5-amino-6-(5- 2.6E−55 MTH_235 riboflavin-specific 1.5E−66 phosphoribosylamino)uracil deaminase reductase MSM0066 Msp_0080 predicted glycosyltransferase 8.2E−107 MTH_590 N-acetylglucosamine-1- 7.9E−107 phosphate transferase MSM0067 NONE NONE MSM0068 Msp_0407 conserved hypothetical protein 6.0E−04 MTH_521 unknown 8.4E−04 MSM0069 Msp_0081 conserved hypothetical protein 2.8E−26 MTH_589 conserved protein 3.1E−25 MSM0070 Msp_0082 conserved hypothetical protein 2.8E−99 MTH_588 conserved protein 4.8E−100 MSM0071 Msp_0083 MetG 5.3E−199 MTH_587 methionyl-tRNA 2.9E−235 synthetase MSM0072 Msp_0216 hypothetical membrane-spanning 2.2E−04 NONE protein MSM0073 Msp_0084 DNA primase, large subunit 1.4E−102 MTH_586 unknown 1.7E−118 MSM0074 NONE NONE MSM0075 Msp_0085 DNA primase, small subunit 1.2E−96 NONE DNA primase, small 8.1E−105 subunit MSM0076 Msp_0710 hypothetical protein 9.9E−04 NONE MSM0077 Msp_0357 putative thymidylate kinase 6.9E−16 MTH_1100 conserved protein 4.6E−47 MSM0078 NONE MTH_1099 conserved protein 3.9E−50 MSM0079 Msp_0392 CofH 7.6E−81 MTH_820 conserved protein 1.0E−106 MSM0080 Msp_0278 ComD 1.0E−53 MTH_1206 phosphonopyruvate 1.7E−47 decarboxylase related protein MSM0081 Msp_0277 ComE 9.4E−51 MTH_1207 phosphonopyruvate 1.7E−40 decarboxylase related protein MSM0082 Msp_0127 HdrA2 1.3E−241 NONE heterodisulfide reductase, 2.5E−133 subunit A MSM0083 Msp_0126 HdrB2 2.6E−94 NONE heterodisulfide reductase, 8.6E−46 subunit B MSM0084 Msp_0125 HdrC2 2.6E−48 NONE heterodisulfide reductase, 3.5E−17 subunit C MSM0085 Msp_1261 conserved hypothetical protein 6.6E−114 MTH_1684 conserved protein 2.1E−115 (contains ferredoxin domain) MSM0086 Msp_1270 ComA 5.2E−73 MTH_1674 conserved protein 3.5E−81 MSM0087 Msp_0233 conserved hypothetical protein 2.3E−22 NONE MSM0088 Msp_1322 conserved hypothetical protein 7.3E−44 MTH_727 conserved protein 1.6E−51 MSM0089 Msp_1314 ProC 8.2E−07 NONE MSM0090 NONE MTH_224 conserved protein 8.6E−30 MSM0091 Msp_0129 putative 2,3-diphosphoglycerate 8.6E−144 MTH_223 unknown 2.0E−172 synthase MSM0092 Msp_0154 member of asn/thr-rich large 5.6E−08 NONE protein family MSM0093 Msp_1068 partially conserved hypothetical 1.1E−58 MTH_1858 phage infection protein 5.7E−98 membrane-spanning protein homolog MSM0094 Msp_0971 hypothetical protein 4.4E−09 MTH_1787 conserved protein 9.3E−17 MSM0095 Msp_1181 predicted phosphotransacetylase 1.3E−44 MTH_231 conserved protein 8.8E−44 MSM0096 Msp_1182 UppS 2.6E−96 MTH_232 conserved protein 2.3E−100 MSM0097 Msp_1183 predicted DNase 3.2E−57 MTH_233 conserved protein 3.4E−67 MSM0098 NONE NONE MSM0099 Msp_0079 hypothetical membrane-spanning 2.1E−23 MTH_596 unknown 8.2E−25 protein MSM0100 Msp_0078 hypothetical membrane-spanning 7.3E−12 MTH_429 unknown 1.1E−13 protein MSM0101 Msp_0988 CbiF 9.8E−88 MTH_602 precorrin-3 methylase 1.5E−80 MSM0102 Msp_1236 MetE 3.4E−69 MTH_775 cobalamin-independent 3.8E−75 methionine synthase MSM0103 NONE MTH_776 conserved protein 7.3E−33 MSM0104 NONE MTH_777 conserved protein 2.7E−42 MSM0105 Msp_1234 conserved hypothetical 3.8E−86 MTH_778 unknown 5.9E−118 membrane-spanning protein MSM0106 Msp_1232 conserved hypothetical protein 1.8E−109 MTH_781 conserved protein 2.3E−132 MSM0107 Msp_1231 HypB 1.4E−79 MTH_782 hydrogenase 1.1E−84 expression/formation protein HypB MSM0108 Msp_1230 HypA 5.8E−35 MTH_783 hydrogenase 4.8E−36 expression/formation protein HypA MSM0109 Msp_0987 hypothetical membrane-spanning 8.6E−09 NONE protein MSM0110 Msp_0017 conserved hypothetical protein 1.5E−22 NONE MSM0111 NONE NONE MSM0112 Msp_0367 predicted helicase 1.2E−208 NONE ATP-dependent RNA 1.4E−235 helicase, elF-4A family MSM0113 Msp_0128 predicted helicase 9.9E−137 MTH_472 DNA helicase II 6.1E−26 MSM0114 NONE NONE MSM0115 Msp_1290 conserved hypothetical protein 8.0E−29 MTH_526 conserved protein 2.1E−51 MSM0116 Msp_1289 conserved hypothetical protein 3.5E−51 MTH_528 unknown 9.1E−42 MSM0117 Msp_1288 conserved hypothetical 4.7E−56 MTH_529 unknown 1.5E−66 membrane-spanning protein MSM0118 Msp_1286 conserved hypothetical protein 1.1E−86 MTH_532 UDP-N-acetylmuramyl 2.9E−86 tripeptide synthetase related protein MSM0119 Msp_0156 predicted nuclease 3.2E−18 MTH_538 unknown 2.5E−14 MSM0120 Msp_1095 DNA double-strand break repair 1.3E−92 MTH_540 intracellular protein 2.1E−27 protein Rad50 transport protein MSM0121 Msp_1094 DNA double-strand break repair 3.7E−72 MTH_541 Rad32 related protein 1.2E−16 protein Mre11 MSM0122 Msp_1093 predicted ATPase 1.7E−122 MTH_307 conserved protein 4.2E−124 MSM0123 Msp_1092 conserved hypothetical protein 2.4E−29 MTH_306 conserved protein 1.2E−32 MSM0124 Msp_1291 PcrB 5.1E−75 MTH_552 conserved protein 2.9E−84 MSM0125 Msp_1292 50S ribosomal protein L40e 5.5E−23 MTH_553 ribosomal protein L40 7.6E−22 MSM0126 Msp_1293 conserved hypothetical protein 9.4E−51 MTH_554 conserved protein 2.9E−54 MSM0127 NONE NONE MSM0128 Msp_0853 conserved hypothetical 2.3E−10 MTH_570 unknown 2.8E−31 membrane-spanning protein MSM0129 Msp_0435 nicotinamide-nucleotide 8.1E−61 MTH_150 conserved protein 6.7E−62 adenylyltransferase MSM0130 NONE MTH_149 molybdenum cofactor 6.6E−39 biosynthesis protein MoaE MSM0131 NONE MTH_920 anion permease 1.5E−04 MSM0132 NONE MTH_1797 conserved protein 7.9E−20 MSM0133 Msp_1198 predicted thioesterase 2.2E−42 MTH_658 unknown 4.8E−36 MSM0134 Msp_0565 predicted M42 glutamyl 2.2E−115 NONE endo-1,4-beta-glucanase 3.7E−116 aminopeptidase MSM0135 Msp_0668 conserved hypothetical protein 9.1E−85 NONE coenzyme F420-reducing 4.5E−88 hydrogenase, beta subunit homolog MSM0136 Msp_0147 ferredoxin 2.2E−06 NONE tungsten 2.2E−06 formylmethanofuran dehydrogenase, subunit G MSM0137 Msp_0220 predicted glycosyltransferase 3.7E−12 MTH_540 intracellular protein 4.7E−05 transport protein MSM0138 NONE MTH_491 conserved protein 2.6E−51 MSM0139 Msp_0448 predicted polysaccharide 7.6E−04 NONE biosynthesis protein MSM0140 Msp_0560 conserved hypothetical protein 4.0E−59 MTH_435 conserved protein 2.9E−68 MSM0141 Msp_0561 predicted dephospho-CoA kinase 5.5E−23 MTH_434 UMP/CMP kinase related 5.6E−42 protein MSM0142 Msp_0563 predicted ATPase of PP-loop 3.2E−66 MTH_432 conserved protein 2.9E−68 superfamily MSM0143 Msp_0564 partially conserved hypothetical 1.3E−30 MTH_431 unknown 2.4E−34 membrane-spanning protein MSM0144 NONE NONE MSM0145 Msp_0451 hypothetical membrane-spanning 1.9E−13 MTH_422 unknown 1.6E−14 protein MSM0146 Msp_0452 conserved hypothetical 7.0E−18 MTH_421 unknown 2.0E−21 membrane-spanning protein MSM0147 Msp_0453 PyrG 2.2E−202 MTH_419 CTP synthase 2.9E−212 MSM0148 Msp_0739 predicted oxidoreductase 3.9E−93 MTH_907 conserved protein 3.1E−32 MSM0149 NONE NONE MSM0150 NONE NONE MSM0151 NONE NONE MSM0152 Msp_1417 predicted Na+-driven multidrug 1.1E−28 MTH_314 conserved protein 4.7E−23 efflux pump MSM0153 Msp_0485 ApgM1 1.3E−110 MTH_418 phosphonopyruvate 2.1E−106 decarboxylase related protein MSM0154 Msp_0487 putative homoserine 1.3E−101 MTH_417 homoserine 6.1E−100 dehydrogenase dehydrogenase homolog MSM0155 Msp_0488 predicted allosteric regulator of 1.1E−29 MTH_416 conserved protein 7.8E−36 homoserine dehydrogenase MSM0156 Msp_0489 conserved hypothetical protein 2.6E−23 MTH_415 conserved protein 3.3E−21 MSM0157 Msp_0484 predicted type I restriction- 1.9E−09 NONE type I restriction 5.3E−09 modification system subunit modification system, subunit S MSM0158 Msp_0483 hypothetical protein 2.3E−17 NONE type I restriction 2.2E−13 modification system, subunit S MSM0159 Msp_0777 member of asn/thr-rich large 2.1E−13 NONE protein family MSM0160 Msp_0490 putative asparagine synthetase 7.9E−102 MTH_414 asparagine synthetase 2.3E−91 MSM0161 NONE NONE MSM0162 NONE NONE MSM0163 Msp_0425 conserved hypothetical protein 7.0E−23 MTH_1083 conserved protein 5.6E−26 MSM0164 Msp_0946 conserved hypothetical protein 1.3E−106 MTH_1084 conserved protein 4.6E−188 MSM0165 Msp_0945 predicted RecB family 7.9E−54 MTH_1085 conserved protein 1.8E−45 exonuclease MSM0166 Msp_0422 predicted helicase 2.3E−27 MTH_1086 conserved protein 9.1E−32 MSM0167 NONE MTH_1087 unknown 8.4E−04 MSM0168 NONE NONE MSM0169 Msp_0220 predicted glycosyltransferase 2.1E−04 NONE MSM0170 Msp_0944 conserved hypothetical protein 1.4E−63 MTH_1091 conserved protein 3.4E−35 MSM0171 Msp_0835 hypothetical membrane-spanning 2.7E−43 MTH_769 unknown 1.7E−34 protein MSM0172 NONE NONE MSM0173 Msp_0145 member of asn/thr-rich large 3.2E−34 MTH_1074 putative membrane 5.5E−31 protein family protein MSM0174 Msp_0677 predicted O-acetylhomoserine 1.9E−123 NONE sulfhydrylase MSM0175 Msp_0676 MetX 2.3E−166 MTH_1820 homoserine O- 1.5E−21 acetyltransferase MSM0176 NONE NONE MSM0177 NONE NONE MSM0178 Msp_1385 conserved hypothetical protein 1.5E−27 NONE MSM0179 NONE NONE MSM0180 NONE MTH_698 unknown 1.6E−04 MSM0181 Msp_1174 50S ribosomal protein L37e 9.6E−26 MTH_648 ribosomal protein L37 2.8E−24 MSM0182 Msp_1175 putative snRNP Sm-like protein 1.5E−27 MTH_649 conserved protein 2.1E−33 MSM0183 Msp_1176 predicted RNA-binding protein 9.0E−46 MTH_650 conserved protein 8.6E−46 MSM0184 Msp_1177 predicted creatinine 1.3E−51 MTH_651 conserved protein 1.6E−51 amidohydrolase MSM0185 Msp_0547 hypothetical membrane-spanning 7.8E−08 MTH_515 unknown 4.3E−05 protein MSM0186 Msp_0345 conserved hypothetical protein 1.3E−14 NONE MSM0187 Msp_0444 rubredoxin 2.5E−09 MTH_156 rubredoxin 2.3E−13 MSM0188 Msp_0444 rubredoxin 3.4E−14 MTH_156 rubredoxin 3.5E−17 MSM0189 Msp_1301 predicted nucleoside- 4.6E−08 MTH_272 acetyl/acyl transferase 1.3E−58 diphosphate-sugar related protein pyrophosphorylase MSM0190 Msp_0617 predicted ATPase 3.1E−84 MTH_271 conserved protein 1.8E−75 MSM0191 Msp_1533 RpoM1 1.5E−04 NONE MSM0192 Msp_0618 ArgH 2.7E−147 MTH_269 argininosuccinate lyase 8.2E−160 MSM0193 Msp_0620 30S ribosomal protein S27Ae 1.8E−17 MTH_268 ribosomal protein S27a 8.1E−18 MSM0194 Msp_0621 30S ribosomal protein S24e 1.1E−26 MTH_267 ribosomal protein S24 1.6E−28 MSM0195 Msp_0622 conserved hypothetical protein 4.8E−31 MTH_266 conserved protein 1.3E−33 MSM0196 Msp_0623 RpoE2 9.0E−14 NONE DNA-dependent RNA 1.5E−18 polymerase, subunit E″ MSM0197 Msp_0624 RpoE1 2.2E−65 NONE DNA-dependent RNA 1.3E−67 polymerase, subunit E′ MSM0198 Msp_0625 inorganic pyrophosphatase 3.1E−68 MTH_263 inorganic 7.2E−65 pyrophosphatase MSM0199 Msp_0626 conserved hypothetical protein 2.4E−22 MTH_262 conserved protein 3.7E−29 MSM0200 Msp_0627 putative translation initiation factor 3.3E−158 NONE translation initiation factor 1.6E−163 2, subunit gamma (alF- elF-2, gamma subunit 2gamma)(elF2G) MSM0201 Msp_0628 30S ribosomal protein S6e 9.9E−40 MTH_260 ribosomal protein S6 1.5E−41 MSM0202 Msp_0629 InfB 9.3E−202 MTH_259 translation initiation factor 2.6E−218 IF2 homolog MSM0203 Msp_0630 nucleoside diphosphate kinase 1.8E−56 MTH_258 nucleoside diphosphate 1.9E−57 kinase MSM0204 Msp_0631 50S ribosomal protein L24e 3.0E−22 MTH_257 ribosomal protein L24 8.2E−25 MSM0205 Msp_0632 30S ribosomal protein S28e 4.3E−30 MTH_256 ribosomal protein S28 2.2E−31 MSM0206 Msp_0633 50S ribosomal protein L7Ae 9.3E−44 MTH_255 ribosomal protein L7a 1.3E−44 MSM0207 NONE MTH_1178 conserved protein 1.9E−41 MSM0208 NONE MTH_1178 conserved protein 3.9E−08 MSM0209 Msp_0861 ferredoxin 7.3E−12 MTH_1106 ferredoxin 7.6E−22 MSM0210 Msp_0253 conserved hypothetical 1.1E−04 NONE membrane-spanning protein MSM0211 NONE NONE MSM0212 NONE NONE MSM0213 Msp_0769 archaeal histone 8.2E−20 MTH_821 histone HMtA1 3.7E−22 MSM0214 Msp_0588 ThrC 2.0E−153 MTH_253 threonine synthase 8.8E−163 MSM0215 Msp_0232 hypothetical membrane-spanning 2.4E−22 MTH_252 conserved protein 4.5E−24 protein MSM0216 Msp_0653 TrpS 5.0E−132 MTH_251 tryptophanyl-tRNA 1.8E−116 synthetase MSM0217 Msp_0652 EndA 5.0E−45 MTH_250 tRNA intron endonuclease 2.7E−49 MSM0218 Msp_0446 predicted metal-dependent 5.3E−57 MTH_214 iron repressor 6.4E−57 transcriptional regulator MSM0219 Msp_1129 partially conserved hypothetical 1.0E−46 MTH_357 conserved protein 4.0E−67 membrane-spanning protein MSM0220 Msp_0114 ThsB 1.7E−170 MTH_218 chaperonin 4.0E−183 MSM0221 Msp_0590 member of asn/thr-rich large 6.9E−13 MTH_719 cell surface glycoprotein 4.2E−05 protein family (s-layer protein) MSM0222 Msp_0787 FprA 2.5E−128 MTH_220 flavoprotein A homolog (II) 3.2E−133 MSM0223 NONE MTH_557 unknown 1.4E−22 MSM0224 NONE MTH_558 unknown 2.1E−28 MSM0225 Msp_1294 conserved hypothetical 1.4E−47 MTH_559 conserved protein 1.4E−54 membrane-spanning protein MSM0226 NONE NONE MSM0227 Msp_0584 HmgA 2.2E−138 MTH_562 3-hydroxy-3- 1.7E−143 methylglutaryl CoA reductase MSM0228 Msp_0583 SucD 1.7E−99 NONE succinyl-CoA synthetase, 1.3E−111 alpha subunit MSM0229 Msp_0582 conserved hypothetical protein 1.6E−69 MTH_564 conserved protein 1.5E−87 MSM0230 Msp_0233 conserved hypothetical protein 2.9E−21 NONE MSM0231 Msp_0577 AroD 9.9E−40 MTH_566 3-dehydroquinate 2.9E−52 dehydratase MSM0232 Msp_0145 member of asn/thr-rich large 3.8E−05 MTH_567 unknown 7.5E−31 protein family MSM0233 Msp_0664 nitrogen regulatory protein P-II 7.9E−31 MTH_664 nitrogen regulatory protein 1.4E−36 P-II MSM0234 Msp_0663 ammonium transporter 4.8E−150 MTH_663 ammonium transporter 1.2E−142 MSM0235 Msp_0119 hypothetical membrane-spanning 6.0E−04 MTH_181 unknown 1.4E−04 protein MSM0236 Msp_0434 predicted phosphohydrolase 1.2E−100 MTH_148 conserved protein 7.8E−123 MSM0237 Msp_0088 predicted 3-polyprenyl-4- 3.1E−59 MTH_147 phenylacrylic acid 2.6E−53 hydroxybenzoate decarboxylase decarboxylase MSM0238 Msp_0087 CbiT 4.2E−48 MTH_146 precorrin-8W 3.1E−48 decarboxylase MSM0239 NONE MTH_145 conserved protein 6.9E−44 MSM0240 Msp_1289 conserved hypothetical protein 8.3E−07 MTH_143 molybdopterin-guanine 1.6E−30 dinucleotide biosynthesis MobA related protein MSM0241 Msp_1252 putative exosome complex, 1.1E−61 MTH_682 conserved protein 5.6E−90 exonuclease 2 subunit MSM0242 Msp_1251 putative exosome complex, 1.4E−79 MTH_683 ribonuclease PH 1.1E−93 exonuclease 1 subunit MSM0243 Msp_1250 putative exosome complex, RNA- 1.6E−48 MTH_684 conserved protein 2.1E−90 binding subunit MSM0244 Msp_1249 conserved hypothetical protein 1.8E−70 MTH_685 conserved protein 8.3E−80 MSM0245 Msp_1248 PsmA 6.3E−77 NONE proteasome, alpha 2.5E−94 subunit MSM0246 Msp_1246 putative ribonuclease P, 1.3E−19 MTH_687 conserved protein 2.3E−22 component 2 MSM0247 Msp_1245 putative ribonuclease P, 2.1E−28 MTH_688 conserved protein 3.1E−41 component 3 MSM0248 Msp_0950 hypothetical protein 7.2E−05 NONE MSM0249 Msp_1548 hypothetical protein 1.8E−04 MTH_301 unknown 4.1E−23 MSM0250 Msp_0501 hypothetical membrane-spanning 1.0E−05 MTH_521 unknown 3.6E−10 protein MSM0251 Msp_0725 hypothetical protein 1.5E−04 NONE MSM0252 Msp_0824 predicted Na+-driven multidrug 1.6E−96 MTH_314 conserved protein 3.7E−93 efflux pump MSM0253 NONE MTH_1725 unknown 1.4E−15 MSM0254 NONE NONE MSM0255 NONE NONE MSM0256 Msp_0017 conserved hypothetical protein 1.7E−28 NONE MSM0257 Msp_0975 hypothetical membrane-spanning 4.3E−30 NONE protein MSM0258 Msp_0724 hypothetical membrane-spanning 1.6E−04 NONE protein MSM0259 Msp_1548 hypothetical protein 1.1E−05 MTH_521 unknown 6.8E−04 MSM0260 Msp_0507 predicted archaea-specific RecJ- 2.0E−199 MTH_763 conserved protein 3.4E−225 like exonuclease MSM0261 Msp_1384 conserved hypothetical 1.1E−04 MTH_759 unknown 1.5E−16 membrane-spanning protein MSM0262 Msp_0788 desulfoferrodoxin 1.4E−26 MTH_757 rubredoxin 3.4E−26 oxidoreductase MSM0263 Msp_1003 predicted NifU protein 1.1E−47 NONE MSM0264 Msp_1002 IscS 6.6E−121 MTH_1389 nifS protein 1.6E−30 MSM0265 Msp_0677 predicted O-acetylhomoserine 1.5E−148 MTH_1188 pleotropic regulatory 3.1E−04 sulfhydrylase protein DegT MSM0266 Msp_0145 member of asn/thr-rich large 2.7E−50 MTH_911 probable surface protein 6.2E−09 protein family MSM0267 Msp_0844 predicted multimeric flavodoxin 4.4E−53 MTH_135 conserved protein 2.7E−17 MSM0268 Msp_0124 CysS 1.2E−139 MTH_587 methionyl-tRNA 9.6E−08 synthetase MSM0269 Msp_0527 conserved hypothetical protein 8.0E−38 NONE MSM0270 Msp_0450 predicted serine acetyltransferase 8.1E−61 MTH_1588 ferripyochelin binding 2.0E−06 protein MSM0271 Msp_0449 cysteine synthase 2.2E−97 NONE tryptophan synthase, beta 3.1E−08 subunit MSM0272 Msp_0497 putative endonuclease III 2.2E−67 MTH_764 endonuclease III 1.1E−70 MSM0273 Msp_0498 AroA 1.1E−102 MTH_766 5-enolpyruvylshikimate 3- 2.5E−62 phosphate synthase MSM0274 NONE NONE MSM0275 Msp_0499 ValS 2.4E−235 MTH_767 valyl-tRNA synthetase 0.0E+00 MSM0276 Msp_0526 hypothetical membrane-spanning 8.1E−29 MTH_768 unknown 2.9E−22 protein MSM0277 Msp_0525 PheT 3.3E−151 MTH_770 phenylalanyl-tRNA 4.2E−172 synthetase MSM0278 NONE NONE MSM0279 Msp_0522 conserved hypothetical protein 4.0E−36 MTH_771 conserved protein 2.7E−35 MSM0280 Msp_0757 predicted ATPase 4.4E−13 NONE MSM0281 Msp_0145 member of asn/thr-rich large 2.1E−09 MTH_911 probable surface protein 2.9E−10 protein family MSM0282 Msp_0141 member of asn/thr-rich large 1.3E−23 MTH_911 probable surface protein 1.1E−17 protein family MSM0283 NONE MTH_436 unknown 1.1E−04 MSM0284 Msp_0995 RpiA 5.8E−74 MTH_608 ribose 5-phosphate 1.3E−74 isomerase MSM0285 Msp_0996 conserved hypothetical protein 1.3E−28 MTH_609 conserved protein 1.3E−35 MSM0286 Msp_0997 EgsA 7.9E−102 MTH_610 glycerol 1-phosphate 1.5E−112 dehydrogenase MSM0287 Msp_1004 ProS 8.6E−160 MTH_611 prolyl-tRNA synthetase 1.4E−155 MSM0288 Msp_1006 conserved hypothetical protein 1.7E−53 MTH_613 conserved protein 4.2E−60 MSM0289 Msp_1007 ThiD 3.6E−58 MTH_614 transcriptional regulator 5.1E−64 MSM0290 Msp_1000 predicted ABC-type 2.6E−71 MTH_920 anion permease 1.4E−31 nitrate/sulfonate/bicarbonate transport system, ATB-binding protein MSM0291 Msp_1001 predicted ABC-type 1.9E−84 MTH_1730 phosphate transporter 4.8E−07 nitrate/sulfonate/bicarbonate permease PstC homolog transport system, permease protein MSM0292 NONE NONE MSM0293 Msp_0826 predicted cation transport ATPase 1.8E−198 MTH_1535 heavy-metal transporting 1.2E−69 CPx-type ATPase MSM0294 Msp_0825 hypothetical protein 4.2E−09 NONE MSM0295 NONE NONE nitrate assimilation 7.1E−49 protein, narQ MSM0296 NONE MTH_691 conserved protein 1.2E−30 MSM0297 Msp_1244 predicted exosome subunit 1.1E−24 MTH_689 conserved protein 2.7E−26 MSM0298 Msp_1243 50S ribosomal protein L15e 2.1E−76 MTH_690 ribosomal protein L15 1.3E−67 MSM0299 NONE NONE MSM0300 Msp_0851 predicted ABC-type 1.5E−139 NONE dipeptide/oligopeptide/nickel transport system, solute-binding protein MSM0301 Msp_0811 ABC-type dipeptide transport 2.3E−120 NONE system, permease protein MSM0302 Msp_0810 ABC-type dipeptide transport 1.7E−99 MTH_1729 phosphate transporter 2.3E−05 system, permease protein permease PstC MSM0303 Msp_0848 predicted ABC-type 3.4E−101 MTH_696 ABC transporter 1.4E−20 dipeptide/oligopeptide/nickel (glutamine transport ATP- transport system, ATP-binding binding protein) protein MSM0304 Msp_0847 predicted ABC-type 4.8E−63 NONE methyl coenzyme M 7.3E−21 dipeptide/oligopeptide/nickel reductase system, transport system, ATP-binding component A2 protein MSM0305 Msp_0431 GuaB 6.1E−10 MTH_406 conserved protein 7.6E−70 MSM0306 Msp_1447 EhbK 3.0E−18 MTH_405 polyferredoxin 1.6E−37 MSM0307 Msp_0071 predicted ribokinase 3.4E−62 MTH_404 ribokinase 3.5E−65 MSM0308 Msp_0070 formylmethanofuran- 6.7E−89 MTH_403 formylmethanofuran: 1.7E−95 tetrahydromethanopterin tetrahydromethanopterin formyltransferase formyltransferase II MSM0309 Msp_0069 conserved hypothetical 2.4E−68 MTH_402 unknown 3.9E−57 membrane-spanning protein MSM0310 Msp_1447 EhbK 1.7E−23 MTH_401 polyferredoxin 7.7E−77 MSM0311 Msp_1447 EhbK 2.1E−13 MTH_399 polyferredoxin 7.4E−111 MSM0312 Msp_1444 EhbN 2.2E−51 NONE formate hydrogenlyase, 7.8E−139 subunit 5 MSM0313 Msp_1445 EhbM 5.4E−32 NONE formate hydrogenlyase, 6.3E−66 subunit 7 MSM0314 NONE MTH_396 conserved protein 2.9E−29 MSM0315 NONE MTH_395 conserved protein 1.9E−18 MSM0316 Msp_0616 partially conserved hypothetical 9.5E−04 MTH_394 unknown 5.8E−08 membrane-spanning protein MSM0317 Msp_1443 EhbO 1.1E−16 NONE NADH dehydrogenase 1.9E−105 (ubiquinone), subunit 1 related protein MSM0318 NONE MTH_392 unknown 1.4E−15 MSM0319 Msp_1452 EhbF 4.0E−06 NONE NADH dehydrogenase I, 5.5E−83 subunit N related protein MSM0320 NONE MTH_390 conserved protein 7.0E−67 MSM0321 NONE MTH_389 conserved protein 6.6E−55 MSM0322 NONE MTH_388 unknown 1.5E−25 MSM0323 NONE MTH_387 conserved protein 3.9E−18 MSM0324 NONE MTH_386 unknown 6.4E−18 MSM0325 NONE MTH_385 conserved protein 4.1E−55 MSM0326 NONE MTH_384 unknown 3.5E−17 MSM0327 Msp_0067 putative UDP-glucose 4- 1.2E−73 MTH_380 UDP-glucose 4-epimerase 1.7E−86 epimerase homolog MSM0328 NONE MTH_698 unknown 2.7E−10 MSM0329 Msp_0265 conserved hypothetical protein 7.4E−51 MTH_700 conserved protein 5.1E−64 MSM0330 Msp_0266 predicted acyl-CoA synthetase 1.1E−184 MTH_701 acetyl-CoA synthetase 1.0E−138 related protein MSM0331 Msp_1390 KorD 7.0E−07 NONE 2-oxoisovalerate 7.9E−20 oxidoreductase, gamma subunit MSM0332 Msp_1389 KorA 1.6E−56 NONE 2-oxoisovalerate 6.4E−144 oxidoreductase, beta subunit MSM0333 Msp_1388 KorB 2.0E−28 NONE 2-oxoisovalerate 8.0E−169 oxidoreductase, alpha subunit MSM0334 Msp_1411 GatD 9.1E−140 MTH_706 L-asparaginase I 6.4E−144 MSM0335 Msp_1412 GatE 8.1E−187 MTH_707 PET112-like protein 7.1E−209 MSM0336 NONE NONE MSM0337 Msp_0145 member of asn/thr-rich large 1.1E−08 NONE protein family MSM0338 NONE NONE MSM0339 NONE NONE MSM0340 Msp_1413 predicted thioredoxin reductase 1.4E−70 MTH_708 thioredoxin reductase 6.9E−92 MSM0341 NONE NONE MSM0342 Msp_0017 conserved hypothetical protein 1.7E−28 NONE MSM0343 Msp_1311 GMP synthase [glutamine 4.2E−64 NONE GMP synthetase, subunit A 1.1E−68 hydrolyzing], subunit A MSM0344 NONE NONE MSM0345 Msp_1312 GMP synthase [glutamine 3.4E−117 NONE GMP synthetase, subunit B 7.1E−122 hydrolyzing], subunit B MSM0346 Msp_1315 conserved hypothetical protein 8.0E−125 MTH_720 unknown 3.1E−128 MSM0347 Msp_1316 conserved hypothetical protein 6.5E−43 MTH_721 conserved protein 8.6E−62 MSM0348 Msp_1317 conserved hypothetical protein 7.1E−14 MTH_722 conserved protein 2.3E−22 MSM0349 Msp_1317 conserved hypothetical protein 1.5E−05 MTH_722 conserved protein 1.2E−04 MSM0350 Msp_1318 predicted 3.9E−155 MTH_723 2-isopropylmalate 6.2E−162 isopropylmalate/homocitrate/citra synthase malate synthase MSM0351 NONE NONE MSM0352 Msp_1319 predicted DNA modification 1.4E−72 MTH_724 methyltransferase related 4.3E−83 methylase protein MSM0353 Msp_1321 hypothetical membrane-spanning 4.8E−11 NONE protein MSM0354 Msp_1206 proteasome-activating 4.1E−144 MTH_728 ATP-dependent 26S 1.2E−172 nucleotidase protease regulatory subunit 4 MSM0355 Msp_1207 predicted transcriptional regulator 7.4E−35 MTH_729 conserved protein 2.7E−33 MSM0356 Msp_1208 conserved hypothetical protein 2.3E−24 MTH_730 conserved protein 6.2E−27 MSM0357 Msp_1209 conserved hypothetical 1.6E−128 MTH_731 unknown 1.5E−110 membrane-spanning protein MSM0358 Msp_1210 conserved hypothetical 7.3E−44 MTH_733 unknown 3.7E−45 membrane-spanning protein MSM0359 Msp_1213 predicted UDP-N-acetylmuramyl 1.7E−108 MTH_530 UDP-N-acetylmuramyl 5.2E−14 tripeptide synthase tripeptide synthase related protein MSM0360 Msp_1214 predicted UDP-N-acetylmuramyl 1.9E−91 MTH_735 phospho-N- 2.8E−102 pentapeptide phosphotransferase acetylmuramoyl- pentapeptide-transferase MSM0361 Msp_1215 partially conserved hypothetical 6.8E−96 MTH_736 conserved protein 2.0E−76 protein, predicted carbamoyl- phosphate synthase, large chain MSM0362 Msp_1216 partially conserved hypothetical 5.4E−16 NONE coenzyme F420-reducing 5.3E−30 protein hydrogenase, delta subunit homolog MSM0363 Msp_1217 predicted RNA methylase 3.2E−50 MTH_738 conserved protein 1.0E−56 MSM0364 Msp_1218 putative nickel responsive 3.0E−54 MTH_739 conserved protein 9.1E−58 regulator MSM0365 Msp_1090 hypothetical protein 2.1E−23 MTH_741 unknown 1.8E−22 MSM0366 NONE NONE MSM0367 Msp_0099 conserved hypothetical protein 6.0E−17 MTH_812 conserved protein 5.6E−26 MSM0368 Msp_0667 putative glutamate synthase, 1.3E−193 NONE glutamate synthase 1.3E−216 subunit 2 with ferredoxin domain (NADPH), alpha subunit MSM0369 Msp_0669 putative glutamate synthase, 1.2E−68 NONE tungsten 1.1E−82 subunit 3 formylmethanofuran dehydrogenase, subunit C homolog MSM0370 Msp_0670 putative glutamate synthase, 5.7E−115 MTH_191 glutamine PRPP 2.2E−127 subunit 1 amidotransferase MSM0371 Msp_0671 predicted glutamine 6.2E−54 MTH_190 conserved protein 3.3E−60 amidotransferase MSM0372 Msp_0673 partially conserved hypothetical 1.3E−23 MTH_187 conserved protein 2.8E−24 protein MSM0373 Msp_1484 LeuB 3.3E−96 MTH_184 isocitrate dehydrogenase 4.5E−104 MSM0374 Msp_0447 predicted acyl-CoA synthetase 8.3E−178 MTH_657 long-chain-fatty-acid-CoA 5.0E−58 ligase MSM0375 Msp_0550 ArgB 2.3E−111 MTH_183 acetylglutamate kinase 2.5E−110 MSM0376 Msp_0967 putative NADP-dependent alcohol 6.2E−06 NONE dehydrogenase MSM0377 Msp_0310 predicted 4.9E−07 MTH_1152 conserved protein 6.5E−05 GTP:adenosylcobinamide- phosphate guanylyltransferase MSM0378 NONE MTH_1876 conserved protein 1.3E−24 MSM0379 Msp_0549 ArgJ 6.5E−107 MTH_182 glutamate N- 1.9E−103 acetyltransferase MSM0380 Msp_0506 hypothetical membrane-spanning 2.1E−05 MTH_181 unknown 1.8E−04 protein MSM0381 Msp_0546 conserved hypothetical 2.8E−99 MTH_180 unknown 1.4E−114 membrane-spanning protein MSM0382 Msp_0545 conserved hypothetical protein 3.7E−95 MTH_179 unknown 1.9E−103 MSM0383 Msp_0544 predicted phosphohydrolase 1.0E−62 MTH_178 lcc related protein 2.6E−53 MSM0384 Msp_0543 conserved hypothetical protein 4.1E−34 MTH_177 conserved protein 1.9E−34 MSM0385 Msp_0511 predicted Fe—S oxidoreductase 3.2E−07 MTH_1784 Mg-protoporphyrin IX 9.9E−84 monomethyl ester oxidative cyclase MSM0386 Msp_0148 predicted sodium:solute 1.9E−178 MTH_1856 sodium/proline symporter 1.5E−181 symporter (proline permease) MSM0387 Msp_1040 coenzyme F390 synthetase II 2.2E−145 MTH_1855 coenzyme F390 1.4E−162 synthetase II MSM0388 Msp_1041 predicted regulatory protein 4.1E−34 MTH_1854 unknown 2.6E−37 MSM0389 Msp_0136 hypothetical protein 1.5E−06 NONE MSM0390 NONE NONE MSM0391 Msp_1042 IorB 5.6E−53 NONE indolepyruvate 2.4E−50 oxidoreductase, beta subunit MSM0392 Msp_1043 IorA 6.7E−185 NONE indolepyruvate 4.1E−192 oxidoreductase, alpha subunit MSM0393 Msp_1044 TfrB 3.3E−135 MTH_1850 fumarate reductase 1.4E−155 MSM0394 Msp_1047 predicted rRNA methylase 2.2E−65 MTH_1849 conserved protein 1.2E−69 MSM0395 Msp_1581 partially conserved hypothetical 2.7E−46 MTH_745 unknown (contains 3.9E−57 protein ferredoxin domain) MSM0396 Msp_0233 conserved hypothetical protein 2.3E−22 NONE MSM0397 NONE NONE MSM0398 Msp_1229 ribose-phosphate 6.6E−04 MTH_1114 uracil 6.6E−23 pyrophosphokinase phosphoribosyltransferase MSM0399 NONE NONE MSM0400 NONE NONE MSM0401 NONE MTH_75 surface protease related 2.7E−27 protein MSM0402 Msp_1048 deoxycytidine triphosphate 3.5E−76 MTH_1847 deoxycytidine 1.1E−75 deaminase triphosphate deaminase MSM0403 Msp_1049 GlyS 2.1E−188 MTH_1846 glycyl-tRNA synthetase 7.6E−196 MSM0404 Msp_0799 predicted transcriptional regulator 1.6E−25 MTH_1843 unknown 9.1E−26 MSM0405 Msp_1050 predicted metal-dependent 1.7E−58 MTH_1842 conserved protein 2.5E−46 hydrolase MSM0406 Msp_1052 hypothetical protein 1.7E−10 MTH_1838 unknown 6.6E−23 MSM0407 Msp_1053 conserved hypothetical 1.7E−115 MTH_1837 unknown 1.2E−124 membrane-spanning protein MSM0408 Msp_0406 2-phosphoglycerate kinase- 4.2E−80 MTH_1835 2-phosphoglycerate 2.3E−91 like/predicted small molecule- kinase homolog binding domain fusion MSM0409 Msp_0407 conserved hypothetical protein 2.2E−42 MTH_1834 conserved protein 9.5E−47 MSM0410 Msp_0409 conserved hypothetical protein 3.9E−52 MTH_1833 unknown 4.6E−47 MSM0411 Msp_0145 member of asn/thr-rich large 1.3E−25 MTH_1074 putative membrane 1.3E−115 protein family protein MSM0412 Msp_0046 member of asn/thr-rich large 1.3E−06 MTH_117 unknown 2.4E−41 protein family MSM0413 Msp_0512 predicted transcriptional regulator 2.7E−21 MTH_313 transcriptional regulator 1.9E−16 MSM0414 Msp_0824 predicted Na+-driven multidrug 2.8E−138 MTH_314 conserved protein 6.7E−110 efflux pump MSM0415 Msp_1362 PyrH 3.5E−76 MTH_879 uridine monophosphate 2.8E−79 kinase MSM0416 Msp_0974 predicted Mg-dependent DNase 1.5E−93 MTH_233 conserved protein 8.0E−27 MSM0417 Msp_1361 hypothetical membrane-spanning 3.8E−15 MTH_880 unknown 3.2E−14 protein MSM0418 Msp_1045 conserved hypothetical protein 2.5E−34 MTH_507 conserved protein 2.5E−32 MSM0419 Msp_0253 conserved hypothetical 1.4E−24 MTH_506 unknown 4.2E−21 membrane-spanning protein MSM0420 Msp_0355 conserved hypothetical 3.0E−22 MTH_882 conserved protein 1.1E−27 membrane-spanning protein MSM0421 NONE NONE MSM0422 Msp_0644 conserved hypothetical 1.1E−36 MTH_883 unknown 6.3E−48 membrane-spanning protein MSM0423 Msp_0645 predicted glycosyltransferase 6.9E−157 MTH_884 teichoic acid biosynthesis 4.5E−184 related protein MSM0424 Msp_1360 transcription initiation factor IIB 8.1E−148 MTH_885 transcription initiation 9.2E−152 (TFIIB) factor TFIIB MSM0425 Msp_1359 hypothetical protein 2.3E−15 MTH_886 conserved protein 3.4E−19 MSM0426 Msp_1358 predicted demethylmenaquinone 3.7E−33 MTH_888 conserved protein 3.2E−46 methyltransferase MSM0427 Msp_1356 predicted DNA primase 7.2E−108 MTH_891 conserved protein 2.9E−141 MSM0428 Msp_1355 predicted site-specific 2.5E−66 MTH_893 integrase-recombinase 7.7E−77 recombinase/integrase protein MSM0429 Msp_1354 conserved hypothetical protein 4.3E−46 MTH_905 conserved protein 1.8E−38 MSM0430 NONE MTH_906 unknown 2.7E−17 MSM0431 Msp_1132 predicted ATP-dependent 1.7E−44 MTH_947 conserved protein 2.8E−40 carboligase MSM0432 Msp_1131 hypothetical membrane-spanning 5.5E−07 NONE protein MSM0433 Msp_1133 AhaD 1.6E−69 NONE ATP synthase, subunit D 1.5E−73 MSM0434 Msp_1134 AhaB 1.4E−212 NONE ATP synthase, subunit B 4.5E−214 MSM0435 Msp_1135 AhaA 1.4E−246 NONE ATP synthase, subunit A 2.8E−260 MSM0436 Msp_1136 AhaF 8.6E−25 NONE ATP synthase, subunit F 3.1E−25 MSM0437 Msp_1137 AhaC 1.5E−105 NONE ATP synthase, subunit C 7.7E−116 MSM0438 Msp_1138 AhaE 3.2E−50 NONE ATP synthase, subunit E 5.9E−54 MSM0439 Msp_1139 AhaK 7.0E−62 NONE ATP synthase, subunit K 9.7E−70 MSM0440 Msp_1140 AhaI 1.9E−148 NONE ATP synthase, subunit I 3.5E−191 MSM0441 Msp_1141 AhaH 7.6E−17 MTH_961 unknown 3.1E−18 MSM0442 NONE NONE MSM0443 NONE NONE MSM0444 NONE NONE MSM0445 Msp_0408 putative nitroreductase protein 2.0E−55 MTH_120 NADPH-oxidoreductase 1.4E−13 MSM0446 NONE MTH_962 citrate synthase I 6.2E−75 MSM0447 Msp_0338 fumarate hydratase 2.6E−15 NONE fumarate hydratase, class 3.8E−75 I related protein MSM0448 NONE MTH_964 unknown 4.6E−102 MSM0449 NONE MTH_965 conserved protein 1.1E−86 MSM0450 Msp_0680 conserved hypothetical 2.4E−38 NONE membrane-spanning protein MSM0451 Msp_0679 conserved hypothetical 7.8E−79 NONE membrane-spanning protein MSM0452 Msp_1142 predicted DNA-binding protein 3.9E−132 MTH_966 conserved protein 1.8E−130 MSM0453 Msp_1143 putative transcriptional regulator 7.5E−58 MTH_967 conserved protein 1.3E−88 MSM0454 NONE NONE MSM0455 Msp_1144 conserved hypothetical protein 2.2E−35 MTH_969 unknown 1.0E−43 MSM0456 Msp_1005 conserved hypothetical protein 2.3E−17 MTH_544 conserved protein 2.7E−35 MSM0457 Msp_1145 SerA 8.8E−158 MTH_970 phosphoglycerate 1.3E−177 dehydrogenase MSM0458 NONE NONE MSM0459 NONE NONE MSM0460 NONE NONE MSM0461 Msp_0983 member of asn/thr-rich large 3.0E−39 MTH_911 probable surface protein 2.9E−18 protein family MSM0462 Msp_1146 partially conserved hypothetical 1.8E−38 MTH_971 unknown 1.0E−33 protein MSM0463 Msp_1147 conserved hypothetical protein 2.0E−57 MTH_972 conserved protein 3.7E−61 MSM0464 Msp_1148 predicted dinucleotide-utilizing 4.0E−59 MTH_973 conserved protein 1.1E−77 protein MSM0465 Msp_1149 conserved hypothetical protein 1.1E−17 MTH_974 unknown 4.1E−23 MSM0466 Msp_1150 predicted tRNA-binding protein 2.4E−68 MTH_975 conserved protein 1.4E−70 MSM0467 NONE MTH_978 NADP-dependent 8.1E−137 glyceraldehyde-3- phosphate dehydrogenase MSM0468 NONE MTH_1490 unknown 2.2E−10 MSM0469 NONE MTH_1490 unknown 1.8E−11 MSM0470 Msp_1151 hypothetical membrane-spanning 1.4E−10 MTH_979 unknown 7.2E−10 protein MSM0471 Msp_1152 conserved hypothetical 7.1E−53 MTH_980 conserved protein 5.9E−70 membrane-spanning protein MSM0472 Msp_1153 PepQ 2.7E−69 MTH_981 aminopeptidase P 1.0E−65 MSM0473 Msp_0417 hypothetical membrane-spanning 2.5E−04 NONE protein MSM0474 NONE NONE MSM0475 Msp_0417 hypothetical membrane-spanning 1.8E−04 NONE protein MSM0476 NONE MTH_93 unknown 8.5E−04 MSM0477 NONE NONE MSM0478 NONE NONE MSM0479 Msp_1154 conserved hypothetical 2.4E−45 MTH_986 conserved protein 2.1E−42 membrane-spanning protein MSM0480 Msp_1155 conserved hypothetical protein 2.3E−95 MTH_987 conserved protein 6.0E−109 MSM0481 Msp_1274 conserved hypothetical protein 4.4E−53 MTH_989 conserved protein 2.2E−24 MSM0482 Msp_1275 predicted ATP-utilizing enzyme 4.6E−58 MTH_990 conserved protein 2.6E−51 MSM0483 NONE MTH_991 unknown 8.6E−14 MSM0484 Msp_1276 conserved hypothetical protein 9.2E−76 MTH_992 inosine-5′- 2.8E−86 monophosphate dehydrogenase related protein IX MSM0485 Msp_1410 predicted universal stress protein 9.6E−26 MTH_993 conserved protein 1.0E−33 MSM0486 Msp_1199 predicted metal-dependent 3.1E−84 MTH_994 N-ethylammeline 4.2E−85 hydrolase chlorohydrolase related protein MSM0487 NONE NONE MSM0488 Msp_1200 CarB 0.0E+00 NONE carbamoyl-phosphate 0.0E+00 synthase, large subunit MSM0489 Msp_1201 CarA 1.5E−121 NONE carbamoyl-phosphate 6.0E−125 synthase, small subunit MSM0490 Msp_0602 conserved hypothetical protein 1.0E−28 MTH_738 conserved protein 3.0E−06 MSM0491 Msp_0410 NadC 2.0E−64 MTH_1832 quinolinate 7.7E−61 phosphoribosyltransferase MSM0492 Msp_0411 putative ribonuclease Z 1.7E−76 MTH_1831 conserved protein 2.6E−92 MSM0493 Msp_0982 predicted mechanosensitive ion 6.7E−25 MTH_1830 conserved protein 1.7E−40 channel MSM0494 Msp_0643 NadA 3.6E−90 MTH_1827 quinolinate synthetase 6.8E−101 MSM0495 NONE MTH_1821 unknown 2.7E−19 MSM0496 Msp_1526 putative homoserine O- 1.2E−84 MTH_1820 homoserine O- 1.3E−67 acetyltransferase acetyltransferase MSM0497 Msp_0157 hypothetical protein 6.9E−55 MTH_1816 conserved protein 2.6E−76 MSM0498 NONE NONE MSM0499 Msp_1548 hypothetical protein 1.0E−05 MTH_1277 unknown 1.8E−06 MSM0500 Msp_0155 predicted amidohydrolase 3.1E−75 MTH_1811 N-carbamoyl-D-amino 3.7E−77 acid amidohydrolase MSM0501 Msp_0153 conserved hypothetical protein 1.8E−31 MTH_1806 phycocyanin alpha 8.1E−34 phycocyanobilin lyase CpcE MSM0502 Msp_0150 predicted helicase 2.9e−310 MTH_1802 ATP-dependent helicase 0.0E+00 MSM0503 Msp_0553 hypothetical protein 9.4E−19 MTH_1799 unknown 3.9E−18 MSM0504 Msp_0927 hypothetical protein 2.1E−05 MTH_1641 unknown 1.4E−06 MSM0505 NONE NONE MSM0506 Msp_0240 predicted ATP-utilizing enzyme 3.0E−148 MTH_1201 conserved protein 3.4E−145 MSM0507 Msp_0365 predicted phosphoesterase 6.0E−49 MTH_1774 conserved protein 2.9E−52 MSM0508 Msp_0364 putative 23S rRNA methylase 1.9E−61 MTH_1773 cell division protein J 5.9E−70 MSM0509 Msp_0363 hypothetical membrane-spanning 1.4E−24 MTH_1772 unknown 9.1E−26 protein MSM0510 Msp_0362 predicted minichromosome 1.4E−255 MTH_1770 DNA replication initiator 1.4E−260 maintenance protein (Cdc21/Cdc54) MSM0511 Msp_0361 translation initiation factor alF-2, 2.3E−54 NONE translation initiation factor 6.9E−60 beta subunit (elF2B) elF-2, beta subunit MSM0512 Msp_0360 predicted NMD3-related protein 5.2E−73 MTH_1768 conserved protein 2.1E−90 MSM0513 Msp_0359 TyrS 2.4E−100 MTH_1767 tyrosyl-tRNA synthetase 1.1E−109 MSM0514 Msp_0358 hypothetical protein 3.5E−05 MTH_1766 unknown 1.1E−08 MSM0515 Msp_0186 MtaB2 1.3E−156 NONE MSM0516 Msp_0185 MtaC3 5.2E−89 NONE MSM0517 Msp_0190 MapA 8.7E−167 MTH_278 ferredoxin 7.0E−04 MSM0518 Msp_0112 MtaA2 2.1E−94 MTH_775 cobalamin-independent 3.4E−05 methionine synthase MSM0519 Msp_0183 hypothetical protein 1.2E−32 NONE MSM0520 Msp_0357 putative thymidylate kinase 2.1E−46 MTH_1765 thymidylate kinase 7.5E−47 MSM0521 NONE NONE MSM0522 Msp_0984 predicted peptidase 2.7E−234 MTH_1763 collagenase 3.4E−99 MSM0523 Msp_0984 predicted peptidase 1.6E−96 MTH_1763 collagenase 6.8E−108 MSM0524 Msp_0354 MutS 4.3E−133 MTH_1762 DNA mismatch 1.9E−176 recognition protein MutS MSM0525 Msp_1282 predicted protein kinase 1.8E−104 MTH_1645 ABC transporter 3.1E−112 MSM0526 NONE NONE MSM0527 Msp_0017 conserved hypothetical protein 3.5E−28 NONE MSM0528 Msp_0233 conserved hypothetical protein 1.4E−10 NONE MSM0529 Msp_0725 hypothetical protein 1.0E−04 NONE MSM0530 Msp_1323 conserved hypothetical protein 3.3E−04 MTH_72 O-linked GlcNAc 5.5E−06 transferase MSM0531 NONE NONE MSM0532 Msp_0233 conserved hypothetical protein 3.4E−08 NONE MSM0533 Msp_0017 conserved hypothetical protein 3.1E−16 NONE MSM0534 NONE NONE MSM0535 Msp_0466 hypothetical protein 7.1E−05 NONE MSM0536 NONE NONE MSM0537 NONE NONE MSM0538 Msp_1324 predicted glycyl radical activating 5.1E−07 MTH_1586 pyruvate formate-lyase 1.3E−05 enzyme activating enzyme MSM0539 Msp_0219 conserved hypothetical protein 3.1E−04 NONE MSM0540 NONE NONE MSM0541 NONE NONE MSM0542 Msp_1128 F420-dependent N5,N10- 3.4E−94 NONE coenzyme F420- 1.4E−132 methylenetetrahydromethanopterin dependent N5,N10- reductase methylene tetrahydromethanopterin reductase MSM0543 Msp_0646 predicted DNA repair photolyase 9.3E−28 NONE MSM0544 Msp_1127 predicted Fe—S oxidoreductase 4.4E−92 MTH_1751 conserved protein 1.3E−90 MSM0545 NONE NONE MSM0546 Msp_1046 hypothetical membrane-spanning 2.6E−23 MTH_813 unknown 2.4E−27 protein MSM0547 Msp_0324 predicted nucleotidyltransferase 1.6E−08 MTH_1749 unknown 7.2E−81 MSM0548 Msp_1148 predicted dinucleotide-utilizing 4.4E−04 MTH_1747 conserved protein 5.4E−37 protein MSM0549 Msp_0830 Trk-type potassium transport 3.9E−04 MTH_1746 cytochrome C-type 2.1E−28 system, membrane protein biogenesis protein MSM0550 Msp_0656 hypothetical membrane-spanning 2.0E−04 MTH_1745 protein disulphide 7.9E−20 protein isomerase MSM0551 Msp_1124 conserved hypothetical protein 1.9E−68 MTH_1744 conserved protein 2.4E−73 MSM0552 Msp_0330 hypothetical protein 4.6E−10 MTH_1743 unknown 8.9E−12 MSM0553 Msp_0331 predicted ATPase 3.5E−92 MTH_1742 conserved protein 1.2E−80 MSM0554 Msp_0161 conserved hypothetical protein 2.8E−74 MTH_1815 conserved protein 2.6E−83 MSM0555 Msp_0192 predicted MoxR-like ATPase 3.9E−93 MTH_1814 conserved protein 1.9E−87 MSM0556 Msp_0333 predicted pterin-binding enzyme 4.1E−121 MTH_1741 conserved protein 1.1E−153 MSM0557 Msp_0334 PorC 2.1E−53 NONE pyruvate oxidoreductase, 2.1E−65 gamma subunit MSM0558 Msp_0335 PorD 4.3E−30 NONE pyruvate oxidoreductase, 1.2E−32 gamma subunit MSM0559 Msp_0336 PorA 2.1E−140 NONE pyruvate oxidoreductase, 2.3E−148 alpha subunit MSM0560 Msp_0337 PorB 1.8E−118 NONE pyruvate oxidoreductase, 2.2E−127 beta subunit MSM0561 Msp_1447 EhbK 8.6E−08 NONE formate hydrogenlyase, 4.5E−40 iron-sulfur subunit I MSM0562 Msp_1447 EhbK 4.0E−09 NONE formate hydrogenlyase, 5.3E−14 iron-sulfur subunit 2 MSM0563 Msp_0338 fumarate hydratase 3.3E−96 NONE fumarate hydratase, class I 8.3E−96 MSM0564 Msp_0339 predicted phosphate uptake 4.8E−31 MTH_1734 phosphate transport 2.8E−47 regulator system regulator MSM0565 Msp_0340 PstB 4.0E−107 MTH_1731 phosphate transport 1.5E−105 system ATP-binding MSM0566 Msp_0341 PstA 1.3E−94 MTH_1730 phosphate transporter 4.5E−111 permease PstC homolog MSM0567 Msp_0342 PstC 7.0E−94 MTH_1729 phosphate transporter 4.8E−100 permease PstC MSM0568 Msp_0343 PstS 1.6E−64 MTH_1727 phosphate-binding protein 2.7E−81 PstS MSM0569 Msp_0344 predicted phosphate uptake 5.5E−62 MTH_1724 phosphate transport 2.4E−82 regulator system regulator related protein MSM0570 Msp_0346 conserved hypothetical 5.2E−17 MTH_1723 unknown 9.1E−26 membrane-spanning protein MSM0571 NONE MTH_1137 conserved protein (FlpA) 5.2E−165 MSM0572 NONE NONE H(2)-dependent N5,N10- 2.4E−128 methylenetetrahydromethanopterin dehydrogenase MSM0573 Msp_0296 CofG 1.4E−15 MTH_1143 biotin synthetase (BioB) 5.1E−112 MSM0574 NONE MTH_1144 conserved protein 2.9E−38 MSM0575 Msp_1393 conserved hypothetical 8.5E−05 MTH_1145 conserved protein 2.9E−38 membrane-spanning protein MSM0576 NONE MTH_1146 conserved protein 2.9E−38 MSM0577 NONE MTH_1147 conserved protein 6.1E−52 MSM0578 NONE MTH_1148 conserved protein 8.1E−34 MSM0579 Msp_1581 partially conserved hypothetical 7.5E−10 MTH_1106 ferredoxin 1.3E−10 protein MSM0580 Msp_0911 member of asn/thr-rich large 2.5E−05 MTH_654 unknown 5.2E−39 protein family MSM0581 Msp_0166 conserved hypothetical 3.9E−29 MTH_655 conserved protein 6.7E−94 membrane-spanning protein MSM0582 Msp_0737 putative peptide methionine 4.5E−122 MTH_535 peptide methionine 2.4E−34 sulfoxide reductase MsrA/MsrB sulfoxide reductase MSM0583 Msp_0655 CbiM2 2.7E−69 MTH_1707 cobalamin biosynthesis 1.5E−64 protein M MSM0584 Msp_0656 hypothetical membrane-spanning 2.2E−12 MTH_1706 unknown 3.4E−12 protein MSM0585 Msp_0657 CbiQ2 5.4E−55 MTH_1705 cobalt transport 4.2E−60 membrane protein MSM0586 Msp_0401 CbiO1 7.6E−81 MTH_1704 cobalt transport ATP- 1.2E−85 binding protein O MSM0587 Msp_1438 hypothetical protein 5.9E−10 NONE MSM0588 Msp_1441 FeoA 1.7E−12 MTH_1362 unknown 2.4E−11 MSM0589 Msp_1440 FeoB 3.6E−200 MTH_1361 ferrous iron transport 5.7E−152 protein B MSM0590 NONE NONE MSM0591 NONE NONE MSM0592 Msp_0202 conserved hypothetical 2.3E−40 MTH_230 unknown 1.2E−48 membrane-spanning protein MSM0593 Msp_0610 predicted ABC-type multidrug 3.9E−77 MTH_1487 ABC transporter (ATP- 2.0E−37 transport system, ATP-binding binding protein MSM0594 Msp_0609 conserved hypothetical 2.7E−44 NONE membrane-spanning protein MSM0595 Msp_0609 conserved hypothetical 1.8E−40 NONE membrane-spanning protein MSM0596 Msp_1163 predicted type II secretion protein F 3.0E−47 MTH_1703 unknown 4.9E−59 MSM0597 Msp_1162 predicted type II/IV secretion 4.1E−121 MTH_1702 secretory protein kinase 2.9E−157 protein MSM0598 Msp_1161 conserved hypothetical protein 3.5E−44 MTH_1701 unknown 5.6E−42 MSM0599 Msp_1160 conserved hypothetical 1.3E−94 MTH_1700 conserved protein 8.9E−99 membrane-spanning protein MSM0600 Msp_0512 predicted transcriptional regulator 7.9E−15 MTH_313 transcriptional regulator 5.5E−12 MSM0601 Msp_0017 conserved hypothetical protein 1.7E−28 NONE MSM0602 Msp_1159 elongation factor 1-beta (aEF- 2.2E−26 MTH_1699 translation elongation 1.3E−28 1beta) (ef1B) factor EF-1b MSM0603 Msp_1158 predicted Zn-ribbon RNA-binding 4.7E−17 MTH_1178 conserved protein 8.3E−04 protein MSM0604 Msp_1157 predicted amino acid kinase 1.7E−42 MTH_1698 delta 1-pyrroline-5- 6.2E−43 carboxylate synthetase MSM0605 Msp_1156 putative peptidyl-tRNA hydrolase 1.5E−29 MTH_1697 conserved protein 1.1E−36 MSM0606 NONE NONE MSM0607 Msp_0613 predicted ATPase 4.1E−224 MTH_1695 RNase L inhibitor 6.8E−227 MSM0608 NONE NONE MSM0609 Msp_0147 ferredoxin 2.6E−04 MTH_221 unknown 6.4E−25 MSM0610 Msp_0370 putative aspartate 8.5E−121 MTH_1694 aspartate 9.6E−134 aminotransferase aminotransferase related protein MSM0611 Msp_0369 RadB 3.9E−61 MTH_1693 DNA repair protein Rad51 3.6E−63 homolog MSM0612 Msp_0096 conserved hypothetical protein 1.9E−36 MTH_1692 conserved protein 3.8E−43 MSM0613 Msp_0095 predicted 1.0E−46 MTH_1691 conserved protein 4.3E−44 phosphatidylglycerophosphate synthase MSM0614 Msp_0094 conserved hypothetical protein 2.1E−14 MTH_1690 unknown 1.7E−17 MSM0615 Msp_0675 conserved hypothetical protein 4.7E−159 MTH_1686 conserved protein 7.7E−164 MSM0616 Msp_0440 member of asn/thr-rich large 1.1E−93 MTH_716 cell surface glycoprotein 1.4E−14 protein family (s-layer protein) MSM0617 Msp_0160 Thil 1.4E−102 MTH_1685 conserved protein 1.1E−118 MSM0618 Msp_1489 predicted potassium transport 3.0E−09 MTH_760 Na+/H+-exchanging 2.3E−16 system, membrane component protein:Na+/H+ antiporter MSM0619 Msp_1262 AlaS 7.0E−300 MTH_1683 alanyl-tRNA synthetase 1.5e−316 MSM0620 Msp_1263 50S ribosomal protein L12P 1.9E−36 MTH_1682 ribosomal protein Lp1 9.4E−40 MSM0621 Msp_1264 50S ribosomal protein L10P 5.3E−96 MTH_1681 ribosomal protein Lp0 2.7E−106 (E. coli) MSM0622 Msp_1265 50S ribosomal protein L1P 9.5E−74 MTH_1680 ribosomal protein L10a 1.3E−81 (E. coli) MSM0623 Msp_1266 50S ribosomal protein L11P 1.3E−62 MTH_1679 ribosomal protein L12 2.2E−63 (E. coli) MSM0624 Msp_1267 putative transcription 1.3E−46 MTH_1678 transcription termination 1.1E−61 antiterminator factor NusG MSM0625 Msp_1268 partially conserved hypothetical 1.3E−12 MTH_1677 protein translocation 1.1E−13 membrane-spanning protein complex sec61 gamma subunit related protein MSM0626 Msp_1269 FtsZ 8.7E−135 MTH_1676 cell division protein FtsZ 1.7E−143 MSM0627 Msp_0307 MtrH 8.5E−105 MTH_1156 N5-methyl- 3.7E−116 tetrahydromethanopterin: coenzyme M methyltransferase, subunit H MSM0628 NONE MTH_1675 conserved protein 7.2E−49 MSM0629 Msp_0017 conserved hypothetical protein 1.7E−28 NONE MSM0630 Msp_1271 conserved hypothetical protein 7.1E−69 MTH_1670 conserved protein 4.2E−76 MSM0631 Msp_1272 predicted transcription initiation 3.4E−37 MTH_1669 conserved protein 4.6E−47 factor IIE, alpha subunit MSM0632 Msp_1273 conserved hypothetical protein 6.2E−38 MTH_1668 conserved protein 1.7E−40 MSM0633 Msp_1063 predicted RNA-binding protein 9.2E−92 MTH_1665 conserved protein 6.9E−92 MSM0634 Msp_1064 conserved hypothetical protein 1.8E−24 MTH_1664 conserved protein 6.2E−27 MSM0635 Msp_1069 predicted regulator of aminoacid 1.6E−41 MTH_1654 unknown 1.8E−45 metabolism MSM0636 Msp_1067 hypothetical protein 1.6E−23 MTH_1649 hydrogenase 1.2E−25 expression/formation protein HypC MSM0637 Msp_1077 predicted dihydrolipoamide 2.4E−93 MTH_1648 dihydrolipoamide 1.2E−92 dehydrogenase-related protein dehydrogenase MSM0638 Msp_1343 hypothetical membrane-spanning 2.6E−78 MTH_1646 unknown 5.9E−54 multicopy protein A 3 MSM0639 Msp_1080 conserved hypothetical 4.5E−67 MTH_1644 unknown 1.8E−52 membrane-spanning protein MSM0640 Msp_1081 predicted release factor aRF1 2.2E−106 MTH_1642 cell division protein 9.6E−118 MSM0641 Msp_1083 putative prephenate 4.4E−92 MTH_1640 chorismate mutase 1.8E−100 dehydrogenase MSM0642 Msp_1084 CdcH 9.3E−273 MTH_1639 cell division control 4.7E−299 protein Cdc48 MSM0643 Msp_0227 conserved hypothetical protein 3.3E−71 MTH_1574 conserved protein 5.2E−78 MSM0644 Msp_0228 ThiC1 1.2E−144 MTH_1576 thiamine biosynthesis 3.2E−158 protein MSM0645 Msp_0258 ATP-dependent DNA ligase 1.1E−148 MTH_1580 DNA ligase 3.9E−176 MSM0646 Msp_0504 conserved hypothetical 5.5E−30 NONE membrane-spanning protein MSM0647 Msp_0259 hypothetical protein 3.8E−15 MTH_1581 conserved protein 4.8E−20 MSM0648 Msp_0263 predicted phosphomannomutase 1.2E−169 MTH_1584 phosphomannomutase 9.9E−171 MSM0649 Msp_0970 hypothetical membrane-spanning 3.5E−44 MTH_559 conserved protein 1.0E−06 protein MSM0650 Msp_0971 hypothetical protein 1.2E−36 MTH_1787 conserved protein 1.3E−07 MSM0651 Msp_1323 conserved hypothetical protein 1.5E−98 MTH_1585 O-linked GlcNAc 1.9E−105 transferase MSM0652 Msp_1324 predicted glycyl radical activating 6.3E−45 MTH_1586 pyruvate formate-lyase 1.5E−50 enzyme activating enzyme MSM0653 Msp_1326 HisC 2.5E−112 MTH_1587 histidinol-phosphate 1.2E−119 aminotransferase MSM0654 Msp_1325 predicted carbonic 1.8E−47 MTH_1588 ferripyochelin binding 4.6E−47 anhydrase/acetyltransferase protein MSM0655 Msp_1301 predicted nucleoside- 3.0E−134 MTH_1589 glucose-1-phosphate 8.1E−137 diphosphate-sugar thymidylyltransferase pyrophosphorylase homolog MSM0656 Msp_1300 predicted phosphomannomutase 9.7E−136 MTH_1590 phosphomannomutase 7.6E−141 MSM0657 Msp_1299 ApgM2 6.1E−150 MTH_1591 phosphonopyruvate 6.0E−148 decarboxylase MSM0658 NONE NONE MSM0659 Msp_1298 conserved hypothetical 4.8E−63 MTH_1592 conserved protein 1.1E−77 membrane-spanning protein MSM0660 Msp_1568 conserved hypothetical 3.9E−52 NONE membrane-spanning protein MSM0661 Msp_1297 30S ribosomal protein S3Ae 3.2E−66 MTH_1593 ribosomal protein S3a 8.4E−71 MSM0662 Msp_0712 hypothetical membrane-spanning 8.9E−07 NONE protein MSM0663 Msp_1295 predicted iron-molybdenum 1.4E−08 MTH_1594 conserved protein 1.2E−16 cluster-binding protein MSM0664 Msp_0540 predicted multimeric flavodoxin 2.4E−22 MTH_1595 conserved protein 5.0E−57 MSM0665 Msp_0642 predicted purine nucleoside 7.4E−74 MTH_1596 methylthioadenosine 3.7E−77 phosphorylase phosphorylase MSM0666 Msp_0641 conserved hypothetical 6.7E−176 MTH_1597 conserved protein 3.5E−184 membrane-spanning protein MSM0667 Msp_0587 hypothetical membrane-spanning 1.8E−05 MTH_520 unknown 3.7E−13 protein MSM0668 Msp_0637 conserved hypothetical protein 4.9E−22 MTH_1598 conserved protein 5.8E−40 MSM0669 NONE NONE MSM0670 NONE NONE MSM0671 Msp_0635 cell division control protein 6-like 2 2.7E−108 MTH_1599 Cdc6 related protein 5.4E−131 MSM0672 Msp_0661 conserved hypothetical protein 1.4E−56 MTH_1600 conserved protein 7.0E−67 MSM0673 Msp_1557 conserved hypothetical 5.1E−27 NONE membrane-spanning protein MSM0674 NONE NONE MSM0675 NONE NONE MSM0676 Msp_1557 conserved hypothetical 9.7E−33 NONE membrane-spanning protein MSM0677 Msp_0662 putative aspartate 1.3E−131 MTH_1601 aspartate 7.3E−136 aminotransferase aminotransferase MSM0678 Msp_0505 conserved hypothetical 8.1E−29 MTH_519 unknown 1.1E−20 membrane-spanning protein MSM0679 Msp_0587 hypothetical membrane-spanning 8.1E−12 MTH_520 unknown 8.1E−34 protein MSM0680 Msp_0757 predicted ATPase 2.4E−109 NONE MSM0681 NONE NONE MSM0682 NONE NONE MSM0683 Msp_0380 hypothetical protein 3.1E−13 MTH_626 unknown 9.7E−22 MSM0684 Msp_0381 hypothetical membrane-spanning 1.2E−09 MTH_625 unknown 1.5E−04 protein MSM0685 NONE NONE MSM0686 Msp_0605 predicted thiamine 2.1E−94 NONE acetolactate synthase, 8.5E−94 pyrophosphate-requiring enzyme large subunit homolog MSM0687 Msp_0604 predicted deoxycytidine 1.6E−57 MTH_1605 deoxycytidine- 8.2E−57 triphosphate deaminase triphosphate deaminase related protein MSM0688 Msp_1409 predicted tautomerase 3.2E−11 MTH_1606 unknown 1.7E−08 MSM0689 NONE NONE MSM0690 Msp_0767 predicted helicase 2.1E−243 NONE ATP-dependent RNA 9.5E−09 helicase, elF-4A family MSM0691 Msp_0006 predicted NUDIX-related protein 1.4E−40 MTH_1336 mutator MutT protein 4.1E−14 homolog MSM0692 NONE NONE MSM0693 Msp_0113 conserved hypothetical protein 1.4E−13 MTH_540 intracellular protein 7.2E−10 transport protein MSM0694 NONE NONE MSM0695 Msp_0767 predicted helicase 1.0E−13 NONE ATP-dependent RNA 3.7E−10 helicase, elF-4A family MSM0696 Msp_1095 DNA double-strand break repair 4.0E−04 NONE protein Rad50 MSM0697 NONE NONE MSM0698 NONE NONE MSM0699 Msp_0738 predicted Na+-dependent 4.1E−137 MTH_1909 unknown 5.8E−04 transporter MSM0700 Msp_0921 putative poly-gamma-glutamate 1.0E−108 NONE biosynthesis protein MSM0701 Msp_0601 partially conserved hypothetical 2.4E−116 MTH_1608 signal recognition particle 3.6E−111 protein, predicted GTPase protein (docking protein) MSM0702 Msp_0600 conserved hypothetical protein 1.5E−20 MTH_1609 conserved protein 1.1E−36 MSM0703 Msp_0599 RplX 4.1E−18 MTH_1610 ribosomal protein L18a 1.0E−17 MSM0704 Msp_0598 translation initiation factor 6 (alF- 3.7E−56 MTH_1611 conserved protein 3.8E−59 6) MSM0705 Msp_0597 50S ribosomal protein L31e 1.4E−22 MTH_1612 ribosomal protein L31 4.7E−29 MSM0706 NONE MTH_1613 ribosomal protein L39 1.2E−16 MSM0707 Msp_0596 predicted subunit of tRNA 2.8E−58 MTH_1614 conserved protein 3.8E−59 methyltransferase MSM0708 Msp_0595 partially conserved hypothetical 1.4E−31 MTH_1615 conserved protein 3.1E−32 protein MSM0709 Msp_0594 30S ribosomal protein S19e 1.5E−52 MTH_1616 ribosomal protein S19 5.9E−54 MSM0710 Msp_0593 hypothetical protein 1.3E−28 MTH_1617 conserved protein 1.3E−19 MSM0711 Msp_0592 putative ribonuclease P, subunit 4 8.7E−32 MTH_1618 conserved protein 3.0E−34 MSM0712 NONE NONE MSM0713 Msp_0589 predicted nucleotide kinase 3.1E−36 MTH_1619 conserved protein 2.4E−34 (adenylate kinase related) MSM0714 Msp_0660 predicted GTPase 2.1E−46 NONE GTP-binding protein, 3.9E−50 GTP1/OBG family MSM0715 Msp_0660 predicted GTPase 2.4E−77 NONE GTP-binding protein, 1.2E−87 GTP1/OBG family MSM0716 Msp_0368 conserved hypothetical 1.1E−141 MTH_1623 oligosaccharyl 7.3E−88 membrane-spanning protein transferase STT3 subunit related protein MSM0717 Msp_0366 TopA 8.0E−228 MTH_1624 DNA topoisomerase I 3.1E−247 MSM0718 NONE MTH_1625 unknown 4.6E−15 MSM0719 Msp_1096 putative phosphoserine 2.7E−124 MTH_1626 phosphoserine 1.3E−83 phosphatase phosphatase MSM0720 Msp_1097 TATA-box binding protein 5.0E−68 MTH_1627 TATA-binding 1.2E−73 transcription initiation factor MSM0721 Msp_1098 predicted adenylate cyclase 2.6E−39 MTH_1629 conserved protein 1.3E−42 MSM0722 Msp_1099 LeuA2 1.9E−91 MTH_1630 2-isopropylmalate 1.5E−151 synthase MSM0723 Msp_1100 LeuC2 2.7E−140 NONE 3-isopropylmalate 5.8E−150 dehydratase, LeuC subunit MSM0724 Msp_0326 hypothetical protein 9.1E−04 MTH_1632 conserved protein 1.0E−40 MSM0725 Msp_1086 flap structure-specific 9.2E−92 MTH_1633 DNA repair protein Rad2 7.8E−100 endonuclease MSM0726 NONE MTH_1635 conserved protein 7.1E−42 MSM0727 Msp_1085 AhcY 1.3E−163 MTH_1636 S-adenosylhomocysteine 3.7E−164 hydrolase MSM0728 Msp_0524 predicted oxidoreductase 4.4E−92 MTH_907 conserved protein 2.5E−62 MSM0729 Msp_0231 predicted E1-like enzyme 2.1E−46 MTH_1571 molybdopterin 1.7E−65 biosynthesis protein MoeB homolog MSM0730 Msp_0017 conserved hypothetical protein 1.7E−28 NONE MSM0731 Msp_0113 conserved hypothetical protein 1.6E−13 MTH_511 DNA helicase II 4.6E−07 MSM0732 Msp_0873 TruB 3.2E−105 MTH_32 centromere/microtubule- 3.2E−110 binding protein MSM0733 Msp_0880 50S ribosomal protein L14e 2.3E−24 MTH_31 ribosomal protein L14 4.1E−23 MSM0734 Msp_0881 putative cytidylate kinase 1.8E−56 MTH_30 cytidylate kinase 3.8E−52 MSM0735 Msp_0882 50S ribosomal protein L34e 2.4E−29 MTH_29 ribosomal protein L34 3.3E−37 (E. coli) MSM0736 Msp_0883 hypothetical membrane-spanning 1.2E−34 MTH_28 conserved protein 1.1E−50 protein MSM0737 Msp_0884 AdkA 1.1E−61 MTH_27 adenylate kinase 1.1E−63 MSM0738 Msp_0885 SecY 6.6E−153 MTH_26 preprotein translocase 1.0E−145 SecY MSM0739 Msp_0886 50S ribosomal protein L15P 1.9E−43 MTH_25 ribosomal protein L27a 4.1E−46 (E. coli) MSM0740 Msp_0887 50S ribosomal protein L30P 9.7E−49 MTH_24 ribosomal protein L7 1.2E−53 (E. coli) MSM0741 Msp_0888 30S ribosomal protein S5P 3.5E−92 MTH_23 ribosomal protein S2 3.7E−93 (E. coli) MSM0742 Msp_0889 50S ribosomal protein L18P 6.7E−57 MTH_22 ribosomal protein L5 8.9E−67 MSM0743 Msp_0890 50S ribosomal protein L19e 4.6E−58 MTH_21 ribosomal protein L19 1.5E−64 MSM0744 Msp_0891 50S ribosomal protein L32e 6.6E−34 MTH_20 ribosomal protein L32 3.1E−41 MSM0745 Msp_0892 50S ribosomal protein L6P 5.7E−60 MTH_19 ribosomal protein L9 4.3E−67 (E. coli) MSM0746 Msp_0893 30S ribosomal protein S8P 9.5E−58 MTH_18 ribosomal protein S15a 1.2E−55 (E. coli) MSM0747 Msp_0894 30S ribosomal protein S14P 2.1E−21 MTH_17 ribosomal protein S29 7.6E−22 (E. coli) MSM0748 Msp_0895 50S ribosomal protein L5P 2.4E−61 MTH_16 ribosomal protein L11 2.9E−61 (E. coli) MSM0749 Msp_0896 30S ribosomal protein S4e 3.0E−70 MTH_15 ribosomal protein S4 1.8E−77 MSM0750 Msp_0897 50S ribosomal protein L24P 2.4E−29 MTH_14 ribosomal protein L26 1.3E−35 (E. coli) MSM0751 Msp_0898 50S ribosomal protein L14P 1.4E−56 MTH_13 ribosomal protein L23 1.0E−56 (E. coli) MSM0752 Msp_0899 30S ribosomal protein S17P 1.4E−42 MTH_12 ribosomal protein S11 1.4E−45 (E. coli) MSM0753 Msp_0900 putative ribonuclease P, 4.8E−24 MTH_11 conserved protein 8.7E−21 component 1 MSM0754 Msp_0901 protein translation factor SUI1-like 2.4E−45 MTH_10 ribosomal protein SUI1 3.6E−47 protein MSM0755 Msp_0902 50S ribosomal protein L29P 3.3E−16 MTH_9 ribosomal protein L35 7.9E−20 (E. coli) MSM0756 Msp_0903 30S ribosomal protein S3P 6.8E−96 MTH_8 ribosomal protein S3 1.2E−96 (E. coli) MSM0757 Msp_0904 50S ribosomal protein L22P 1.3E−46 MTH_7 ribosomal protein L17 3.5E−56 (E. coli) MSM0758 Msp_0905 30S ribosomal protein S19P 1.4E−58 MTH_6 ribosomal protein S15 1.3E−58 (E. coli) MSM0759 Msp_0906 50S ribosomal protein L2P 3.1E−107 MTH_5 ribosomal protein L8 1.9E−105 (E. coli) MSM0760 Msp_0907 50S ribosomal protein L23P 2.8E−26 MTH_4 ribosomal protein L23a 5.4E−28 (E. coli) MSM0761 Msp_0908 50S ribosomal protein L1e 4.5E−99 MTH_3 ribosomal protein L4 2.6E−99 (E. coli) MSM0762 Msp_0909 50S ribosomal protein L3P 1.5E−121 MTH_2 ribosomal protein L3 1.1E−132 (E. coli) MSM0763 Msp_0910 conserved hypothetical protein 1.1E−79 MTH_1 conserved protein 1.2E−73 MSM0764 Msp_1319 predicted DNA modification 1.7E−04 MTH_1918 possible protein 3.7E−45 methylase methyltransferase MSM0765 Msp_0914 PycA 1.7E−186 MTH_1917 biotin carboxylase 5.5E−202 MSM0766 Msp_0915 partially conserved hypothetical 4.0E−36 MTH_1916 biotin acetyl-CoA 5.3E−62 protein carboxylase ligase/biotin operon repressor MSM0767 Msp_0916 predicted selenocysteine 2.8E−99 MTH_1914 conserved protein 2.3E−100 synthase MSM0768 Msp_0917 hypothetical protein 7.5E−04 MTH_1912 unknown 1.1E−11 MSM0769 Msp_0791 fumarate hydratase 3.1E−59 NONE fumarate hydratase, class 1.5E−50 I related protein MSM0770 Msp_1112 CbiO2 1.2E−43 NONE methyl coenzyme M 8.3E−64 reductase system, component A2 homolog MSM0771 Msp_0657 CbiQ2 1.4E−05 MTH_453 conserved protein 2.6E−12 MSM0772 NONE MTH_452 unknown 9.2E−07 MSM0773 Msp_0958 predicted ABC-type polar amino 1.4E−26 MTH_1704 cobalt transport ATP- 5.9E−25 acid transport system, ATP- binding protein O binding protein MSM0774 Msp_0340 PstB 1.6E−26 MTH_1731 phosphate transport 5.2E−26 system ATP-binding MSM0775 Msp_0149 predicted transcriptional regulator 2.0E−34 NONE MSM0776 Msp_0790 conserved hypothetical 2.2E−138 MTH_1909 unknown 2.8E−159 membrane-spanning protein MSM0777 Msp_0491 hypothetical membrane-spanning 3.6E−10 MTH_1908 unknown 3.2E−16 protein MSM0778 Msp_0517 predicted RNA-binding protein 3.6E−184 MTH_1907 conserved protein 2.0E−188 MSM0779 Msp_0516 predicted Zn-dependent 2.3E−70 MTH_1902 conserved protein 3.5E−72 hydrolase of the beta-lactamase superfamily MSM0780 NONE MTH_1901 unknown 2.9E−16 MSM0781 Msp_1151 hypothetical membrane-spanning 1.2E−09 MTH_1533 unknown 1.3E−10 protein MSM0782 Msp_1151 hypothetical membrane-spanning 2.4E−04 MTH_979 unknown 1.2E−05 protein MSM0783 Msp_1447 EhbK 3.3E−20 NONE tungsten 3.5E−88 formylmethanofuran dehydrogenase, subunit F homolog MSM0784 Msp_0236 ferredoxin 5.5E−14 MTH_927 ferredoxin 5.1E−16 MSM0785 Msp_0514 putative phosphopantetheine 1.0E−37 MTH_1896 conserved protein 1.3E−42 adenylyltransferase MSM0786 Msp_1129 partially conserved hypothetical 1.1E−49 MTH_412 conserved protein 1.3E−69 membrane-spanning protein MSM0787 Msp_0511 predicted Fe—S oxidoreductase 7.6E−120 MTH_1895 conserved protein 8.7E−124 MSM0788 Msp_0510 putative aspartate 5.5E−117 MTH_1894 aspartate 3.3E−108 aminotransferase aminotransferase homolog MSM0789 Msp_0519 predicted Co/Zn/Cd cation 7.6E−33 MTH_1893 cation efflux system 1.8E−77 transporter protein (zinc/cadmium) MSM0790 Msp_1428 conserved hypothetical protein 1.3E−15 MTH_1884 conserved protein 3.0E−36 MSM0791 Msp_0443 2-phosphoglycerate kinase 3.6E−81 MTH_1883 2-phosphoglycerate 3.7E−84 kinase MSM0792 Msp_1010 predicted phosphoesterase 1.8E−47 MTH_1882 conserved protein 2.3E−52 MSM0793 Msp_1011 conserved hypothetical protein 1.9E−29 MTH_1881 conserved protein 4.4E−42 MSM0794 Msp_1012 conserved hypothetical protein 1.9E−20 MTH_1880 conserved protein 2.1E−28 MSM0795 Msp_1013 HdrB1 1.9E−116 NONE heterodisulfide reductase, 4.3E−115 subunit B MSM0796 Msp_1014 HdrC1 1.6E−69 NONE heterodisulfide reductase, 4.7E−77 subunit C MSM0797 Msp_1015 conserved hypothetical protein 2.5E−50 MTH_1877 conserved protein 1.6E−53 MSM0798 NONE NONE MSM0799 Msp_0113 conserved hypothetical protein 1.6E−12 MTH_1626 phosphoserine 2.2E−06 phosphatase MSM0800 NONE NONE MSM0801 Msp_1017 DphB 1.7E−74 MTH_1874 diphthine synthase 2.9E−77 MSM0802 Msp_1022 predicted methyltransferase 3.6E−81 MTH_1873 met-10+ protein 1.3E−74 MSM0803 NONE MTH_633 conserved protein 4.3E−04 MSM0804 Msp_1023 putative translation initiation factor 5.0E−100 NONE translation initiation factor 2.2E−125 alF-2B, subunit 1 elF-2B, alpha subunit MSM0805 Msp_0958 predicted ABC-type polar amino 5.0E−100 MTH_696 ABC transporter 2.7E−35 acid transport system, ATP- (glutamine transport ATP- binding protein binding protein) MSM0806 Msp_0959 predicted ABC-type polar amino 2.1E−92 NONE acid transport system, permease protein MSM0807 Msp_0960 predicted ABC-type polar amino 3.5E−108 NONE acid transport system, periplasmic substrate-binding protein MSM0808 Msp_1024 conserved hypothetical protein 2.9E−104 MTH_1871 nitrogenase iron- 1.6E−115 molybdenum cofactor biosynthesis protein NifB MSM0809 Msp_1025 conserved hypothetical protein 2.3E−40 MTH_1870 conserved protein 3.1E−41 MSM0810 Msp_1026 predicted activator of 2- 5.5E−165 MTH_1869 activator of (R)-2- 1.7E−175 hydroxyglutaryl-CoA dehydratase hydroxyglutaryl-CoA MSM0811 Msp_1027 conserved hypothetical protein 1.7E−53 MTH_1868 conserved protein 1.2E−57 MSM0812 Msp_1029 conserved hypothetical protein 1.3E−39 MTH_1866 conserved protein 1.0E−40 MSM0813 Msp_1030 predicted peptidyl-prolyl cis-trans 2.6E−135 MTH_1865 conserved protein 2.3E−146 isomerase MSM0814 Msp_1032 predicted selenophosphate 3.3E−87 MTH_1864 phosphoribosylformylglycinamidine 6.2E−91 synthetase-related protein synthase II related protein MSM0815 Msp_1033 conserved hypothetical protein 4.5E−99 MTH_1863 conserved protein 4.4E−97 MSM0816 Msp_1034 predicted nucleic acid-binding 3.7E−33 MTH_1862 conserved protein 3.5E−40 protein MSM0817 Msp_0799 predicted transcriptional regulator 6.6E−34 MTH_1843 unknown 1.0E−33 MSM0818 Msp_0798 predicted transcriptional regulator 5.0E−36 MTH_1843 unknown 2.1E−26 MSM0819 NONE MTH_1438 unknown 4.6E−15 MSM0820 NONE MTH_1861 molybdenum cofactor 2.5E−46 biosynthesis MoaB MSM0821 Msp_1036 PyrE 3.1E−59 MTH_1860 uridine 5′- 5.2E−55 monophosphate synthase MSM0822 Msp_1035 hypothetical protein 3.1E−13 MTH_1859 unknown 1.4E−15 MSM0823 NONE NONE MSM0824 NONE NONE N-terminal 3.1E−06 acetyltransferase complex, subunit ARD1 MSM0825 Msp_0437 conserved hypothetical protein 4.7E−56 NONE MSM0826 Msp_0114 ThsB 8.2E−226 MTH_794 chaperonin 2.4E−231 MSM0827 Msp_0747 member of asn/thr-rich large 5.9E−04 MTH_796 conserved protein 4.5E−33 protein family MSM0828 Msp_0220 predicted glycosyltransferase 2.0E−14 MTH_540 intracellular protein 8.1E−06 transport protein MSM0829 Msp_0110 aspartate-semialdehyde 6.6E−121 MTH_799 aspartate-semialdehyde 2.3E−132 dehydrogenase dehydrogenase MSM0830 Msp_0109 DapB 1.0E−85 MTH_800 dihydrodipicolinate 3.2E−87 reductase MSM0831 Msp_0108 DapA 4.9E−86 MTH_801 dihydrodipicolinate 2.0E−85 synthase MSM0832 Msp_0107 putative aspartokinase 2.2E−129 MTH_802 aspartokinase II alpha 6.7E−149 subunit MSM0833 Msp_0106 30S ribosomal protein S17e 1.3E−19 MTH_803 ribosomal protein S17 1.5E−23 MSM0834 Msp_0105 putative chorismate mutase 3.8E−15 NONE chorismate mutase, 9.3E−17 subunit A MSM0835 Msp_0104 AroK 4.7E−56 MTH_805 conserved protein 2.6E−76 (homoserine kinase related) MSM0836 Msp_0101 predicted glycosyltransferase 2.6E−64 MTH_450 LPS biosynthesis RfbU 9.6E−31 related protein MSM0837 Msp_0102 CbiD 6.5E−91 MTH_808 cobalamin biosynthesis 4.0E−87 protein D MSM0838 Msp_0103 putative thioredoxin 2.5E−18 MTH_807 thioredoxin 7.1E−19 MSM0839 Msp_0100 predicted helicase 2.1E−227 MTH_810 DNA helicase related 9.1E−248 protein MSM0840 Msp_0097 conserved hypothetical protein 3.0E−15 MTH_814 conserved protein 1.6E−14 MSM0841 Msp_0371 hypothetical protein 6.6E−11 MTH_815 unknown 2.2E−15 MSM0842 Msp_0372 predicted histone 1.5E−187 MTH_817 conserved protein 6.2E−189 acetyltransferase MSM0843 NONE MTH_818 deoxyribose-phosphate 2.1E−26 aldolase MSM0844 Msp_0122 archaeal histone 3.5E−21 MTH_821 histone HMtA1 2.5E−23 MSM0845 Msp_0376 predicted 2-methylthioadenine 8.9E−126 MTH_826 conserved protein 3.8E−130 synthetase MSM0846 Msp_0375 conserved hypothetical protein 1.6E−39 MTH_828 conserved protein 1.6E−46 MSM0847 Msp_0374 LeuD2 4.1E−57 NONE 3-isopropylmalate 7.4E−56 dehydratase, LeuD subunit MSM0848 Msp_0373 predicted archaeal sugar kinase 1.5E−73 MTH_830 conserved protein 3.0E−82 MSM0849 Msp_0384 predicted Fe—S oxidoreductase 6.6E−169 MTH_831 molybdenum cofactor 2.7E−177 biosynthesis MoaA homolog MSM0850 Msp_0385 conserved hypothetical 2.4E−45 MTH_832 conserved protein 1.4E−43 membrane-spanning protein MSM0851 Msp_0386 predicted transcriptional regulator 1.1E−70 MTH_834 conserved protein 3.0E−98 MSM0852 Msp_0387 predicted ATP-utilizing enzyme 2.3E−40 MTH_835 conserved protein 1.0E−53 MSM0853 Msp_0217 predicted UDP-N- 1.4E−120 MTH_837 UDP-N- 1.3E−136 acetylglucosamine 2-epimerase acetylglucosamine 2- epimerase MSM0854 NONE NONE MSM0855 Msp_0388 TruA 5.2E−50 MTH_840 pseudouridylate synthase I 1.6E−51 MSM0856 NONE MTH_695 conserved protein 1.7E−08 MSM0857 Msp_1000 predicted ABC-type 1.5E−29 MTH_696 ABC transporter 3.3E−44 nitrate/sulfonate/bicarbonate (glutamine transport ATP- transport system, ATB-binding binding protein) protein MSM0858 Msp_0389 HisA 6.3E−77 MTH_843 phosphoribosylformimino- 7.4E−79 5-aminoimidazole carboxamide ribotide isomerase MSM0859 Msp_0390 putative cytidylyltransferase 5.1E−43 MTH_844 autotrophic growth 1.5E−48 protein MSM0860 Msp_0552 ArgC 4.9E−109 MTH_846 N-acetyl-gamma-glutamyl- 2.0E−108 phosphate reductase MSM0861 Msp_0554 hypothetical protein 4.8E−31 MTH_847 unknown 3.3E−44 MSM0862 Msp_0521 PyrI 2.1E−44 MTH_850 aspartate 7.5E−47 carbamoyltransferase regulatory subunit MSM0863 Msp_1419 hypothetical protein 3.1E−20 NONE MSM0864 NONE MTH_1285 conserved protein 2.7E−10 MSM0865 Msp_0159 conserved hypothetical protein 1.1E−79 MTH_853 conserved protein 2.4E−96 MSM0866 Msp_0402 predicted zinc metalloprotease 4.7E−143 MTH_856 zinc metalloproteinase 8.2E−144 MSM0867 Msp_0403 conserved hypothetical protein 1.1E−47 MTH_857 conserved protein 4.0E−48 MSM0868 NONE NONE MSM0869 Msp_0404 predicted GTPase 3.0E−93 NONE GTP-binding protein, 8.2E−112 GTP1/OBG family MSM0870 Msp_0405 putative small heat shock protein 1.2E−16 NONE heat shock protein, class I 3.8E−20 MSM0871 Msp_0017 conserved hypothetical protein 1.7E−28 NONE MSM0872 Msp_1054 predicted phosphosugar 1.2E−103 MTH_860 glucosamine-fructose-6- 5.6E−113 isomerase phosphate aminotransferase MSM0873 Msp_1309 conserved hypothetical protein 7.6E−17 MTH_863 conserved protein 5.4E−28 MSM0874 Msp_1308 adenine deaminase 1.5E−139 MTH_866 adenine deaminase 1.3E−132 MSM0875 Msp_1347 conserved hypothetical protein 6.0E−136 MTH_867 conserved protein 6.4E−144 MSM0876 Msp_0415 predicted 1.3E−71 MTH_868 agmatine ureohydrolase 1.2E−73 arginase/agmatinase/formimionoglutamate hydrolase MSM0877 Msp_1352 translation initiation factor 5A (alF- 4.4E−53 NONE translation initiation factor, 1.7E−49 5A) elF-5A MSM0878 Msp_1327 PdaD 2.1E−37 MTH_870 conserved protein 3.4E−42 MSM0879 Msp_1330 PpnK 7.2E−60 MTH_872 conserved protein 9.0E−77 MSM0880 Msp_1331 predicted UDP-N-acetylmuramyl 1.1E−47 MTH_873 UDP-N-acetylmuramyl 5.4E−81 pentapeptide synthase tripeptide synthetase related protein MSM0881 Msp_1332 HemC 7.3E−83 MTH_874 porphobilinogen 2.0E−85 deaminase MSM0882 Msp_1333 predicted dehydrogenase 2.7E−101 NONE 3-chlorobenzoate-3,4- 3.0E−130 dioxygenase dyhydrogenase related protein MSM0883 Msp_1334 predicted orotate 5.6E−53 MTH_876 orotate 9.7E−70 phosphoribosyltransferase phosphoribosyltransferase MSM0884 Msp_0747 member of asn/thr-rich large 1.5E−18 MTH_716 cell surface glycoprotein 4.1E−07 protein family (s-layer protein) MSM0885 Msp_1465 member of asn/thr-rich large 2.4E−39 MTH_716 cell surface glycoprotein 1.7E−08 protein family (s-layer protein) MSM0886 NONE NONE MSM0887 Msp_1410 predicted universal stress protein 2.5E−18 MTH_898 conserved protein 1.5E−18 MSM0888 Msp_1416 GdhA 2.6E−181 NONE MSM0889 NONE NONE MSM0890 NONE NONE MSM0891 Msp_1363 peptide chain release factor, 3.4E−149 NONE peptide chain release 8.7E−156 subunit 1 (aRF-1) factor eRF, subunit 1 MSM0892 Msp_1056 hypothetical membrane-spanning 5.4E−06 MTH_1905 unknown 3.2E−06 protein MSM0893 Msp_1202 predicted acetyltransferase 2.4E−29 NONE N-terminal 3.7E−38 acetyltransferase complex, subunit ARD1 MSM0894 Msp_1203 conserved hypothetical protein 5.7E−28 MTH_1000 conserved protein 1.2E−25 MSM0895 Msp_1204 predicted cation transport ATPase 3.9E−235 MTH_1001 cation-transporting P- 9.8E−251 ATPase PacL MSM0896 Msp_1205 CbiJ 6.5E−43 MTH_1002 cobalamin biosynthesis 8.5E−39 protein J MSM0897 Msp_1365 30S ribosomal protein S10P 1.6E−48 MTH_1059 ribosomal protein S20 1.3E−49 (E. coli) MSM0898 Msp_1366 translation elongation factor 1- 1.9E−185 NONE translation elongation 3.9E−192 alpha (EF-Tu) factor, EF-1 alpha MSM0899 Msp_1367 FusA 1.7e−319 NONE translation elongation 1.9e−318 factor, EF-2 MSM0900 Msp_1368 30S ribosomal protein S7P 3.3E−80 MTH_1056 ribosomal protein S5 9.2E−81 (E. coli) MSM0901 Msp_1369 30S ribosomal protein S12P 4.4E−69 MTH_1055 ribosomal protein S23 7.8E−68 (E. coli) MSM0902 Msp_0321 MrtA 5.7E−250 NONE methyl coenzyme M 2.0E−250 reductase II, alpha subunit MSM0903 Msp_0320 MrtG 1.6E−103 NONE methyl coenzyme M 1.8E−116 reductase II, gamma subunit MSM0904 Msp_0319 MrtD 1.9E−45 NONE methyl coenzyme M 2.2E−40 reductase II, D protein MSM0905 Msp_0318 MrtB 9.8E−159 NONE methyl coenzyme M 4.1E−181 reductase II, beta subunit MSM0906 Msp_1370 NusA 1.7E−44 MTH_1054 transcription termination 2.5E−55 factor NusA MSM0907 Msp_1371 50S ribosomal protein L30e 6.0E−33 MTH_1053 ribosomal protein L30 3.0E−36 MSM0908 Msp_1372 RpoA2 2.1E−126 NONE DNA-dependent RNA 4.7E−141 polymerase, subunit A″ MSM0909 Msp_1373 RpoA1 0.0E+00 NONE DNA-dependent RNA 0.0E+00 polymerase, subunit A′ MSM0910 Msp_1374 RpoB1 6.1E−253 NONE DNA-dependent RNA 4.6E−276 polymerase, subunit B′ MSM0911 Msp_1375 RpoB2 3.3E−103 NONE DNA-dependent RNA 8.6E−220 polymerase, subunit B″ MSM0912 Msp_1376 RpoH 7.6E−17 NONE DNA-dependent RNA 4.6E−15 polymerase, subunit H MSM0913 NONE NONE MSM0914 NONE MTH_72 O-linked GlcNAc 3.0E−04 transferase MSM0915 NONE NONE MSM0916 Msp_0682 ThiM1 1.2E−73 NONE MSM0917 Msp_0683 hypothetical protein 7.7E−56 NONE MSM0918 Msp_1381 phosphoglycerate kinase 1.1E−120 MTH_1042 3-phosphoglycerate 4.3E−131 kinase MSM0919 Msp_1382 TpiA 4.9E−77 MTH_1041 triosephosphate 3.2E−71 isomerase MSM0920 Msp_1103 member of asn/thr-rich large 4.2E−04 NONE protein family MSM0921 Msp_0548 hypothetical membrane-spanning 1.1E−05 NONE protein MSM0922 Msp_1383 predicted Fe—S oxidoreductase 1.7E−97 MTH_1039 conserved protein 4.9E−98 MSM0923 Msp_0540 predicted multimeric flavodoxin 1.2E−16 MTH_135 conserved protein 1.3E−17 MSM0924 Msp_1386 SucC 3.4E−101 NONE succinyl-CoA synthetase, 3.7E−116 beta subunit MSM0925 Msp_1387 KorC 9.5E−58 NONE 2-oxoglutarate 8.8E−60 oxidoreductase, gamma subunit MSM0926 Msp_1388 KorB 1.3E−99 NONE 2-oxoglutarate 2.2E−102 oxidoreductase, beta subunit MSM0927 Msp_1389 KorA 4.5E−138 NONE 2-oxoglutarate 6.2E−130 oxidoreductase, alpha subunit MSM0928 Msp_1390 KorD 3.0E−15 NONE ferredoxin (putative 2- 8.6E−14 oxoglutarate oxidoreductase, delat subunit) MSM0929 Msp_0791 fumarate hydratase 3.7E−17 NONE fumarate hydratase, class I 3.5E−40 MSM0930 Msp_0325 predicted peptidyl-prolyl cis-trans 3.5E−67 MTH_1125 fkbp-type peptidyl-prolyl 1.8E−77 isomerase 2 cis-trans isomerase MSM0931 Msp_0801 conserved hypothetical protein 7.0E−94 MTH_448 unknown 4.8E−68 MSM0932 Msp_1167 conserved hypothetical protein 4.7E−49 MTH_1113 conserved protein 1.6E−58 MSM0933 Msp_1168 CobS 1.2E−50 MTH_1112 cobalamin (5′-phosphate) 1.9E−41 synthase MSM0934 Msp_1169 hypothetical protein 1.1E−06 MTH_1111 conserved protein 1.5E−41 MSM0935 Msp_1170 conserved hypothetical protein 4.5E−106 MTH_1109 conserved protein 4.2E−92 MSM0936 Msp_1171 predicted ATPase 6.3E−77 MTH_1108 conserved protein 1.0E−65 MSM0937 NONE NONE MSM0938 NONE NONE MSM0939 Msp_1173 PycB 1.4E−212 NONE oxaloacetate 2.8E−221 decarboxylase, alpha subunit MSM0940 Msp_1166 predicted myo-inositol-1- 5.3E−151 MTH_1105 conserved protein 9.4E−159 phosphate synthase MSM0941 Msp_0634 predicted prenyltransferase 2.3E−70 MTH_1098 bacteriochlorophyll 4.2E−69 synthase related protein MSM0942 Msp_0616 partially conserved hypothetical 5.0E−52 MTH_371 unknown 5.1E−35 membrane-spanning protein MSM0943 NONE MTH_466 unknown 5.6E−09 MSM0944 NONE NONE MSM0945 Msp_1285 hydrogenase 9.3E−147 MTH_1072 hydrogenase 2.2E−141 expression/formation protein expression/formation protein HypD MSM0946 Msp_0215 predicted glycosyltransferase 6.1E−04 MTH_1071 conserved protein 3.9E−50 MSM0947 Msp_1284 predicted modulator of DNA 3.7E−95 MTH_1070 conserved protein 1.5E−96 gyrase MSM0948 Msp_0220 predicted glycosyltransferase 4.0E−04 NONE MSM0949 Msp_1351 predicted transcriptional activator 6.7E−18 MTH_628 unknown 1.6E−19 MSM0950 NONE MTH_1003 molybdenum cofactor 6.8E−101 biosynthesis protein MoeA MSM0951 Msp_1335 translation initiation factor 1A (alF- 1.6E−41 NONE translation initiation factor, 1.3E−44 1A) (elF1A) elF-1A MSM0952 Msp_1337 predicted serine/threonine protein 5.1E−59 MTH_1005 conserved protein 1.1E−75 kinase MSM0953 NONE MTH_630 unknown 1.5E−04 MSM0954 Msp_1338 predicted RNA-binding protein 1.4E−56 MTH_1006 conserved protein 2.0E−60 MSM0955 Msp_1339 type II DNA topoisomerase VI, 2.4E−203 MTH_1007 conserved protein 1.5E−213 subunit B MSM0956 Msp_1340 type II DNA topoisomerase VI, 4.3E−149 MTH_1008 conserved protein 1.8E−155 subunit A MSM0957 Msp_0119 hypothetical membrane-spanning 6.8E−20 MTH_524 unknown 4.9E−35 protein MSM0958 Msp_1110 CobN 5.3E−11 MTH_515 unknown 1.1E−08 MSM0959 Msp_0994 conserved hypothetical protein 3.0E−31 NONE MSM0960 Msp_0678 predicted cation transport ATPase 4.8E−134 MTH_411 cadmium efflux ATPase 1.9E−80 MSM0961 Msp_0224 predicted cation transport ATPase 9.6E−07 MTH_1535 heavy-metal transporting 1.4E−08 CPx-type ATPase MSM0962 Msp_1346 glyceraldehyde 3-phosphate 4.7E−127 MTH_1009 glyceraldehyde 3- 5.9E−134 dehydrogenase phosphate dehydrogenase MSM0963 Msp_0992 putative endonuclease IV 9.5E−06 MTH_1010 endonuclease IV 6.6E−71 MSM0964 Msp_1349 predicted phosphohydrolase 8.0E−19 MTH_1179 conserved protein 1.1E−38 MSM0965 Msp_0718 preducted 3-hydroxyacyl-CoA 2.6E−126 NONE dehydrogenase MSM0966 Msp_1415 putative 26S protease, regulatory 6.5E−107 MTH_1011 ATP-dependent 26S 7.4E−111 subunit protease regulatory subunit 8 MSM0967 Msp_1408 HemA 4.6E−90 MTH_1012 glutamyl-tRNA reductase 3.2E−94 MSM0968 Msp_1407 predicted siroheme synthase 2.4E−45 MTH_1013 conserved protein 1.9E−41 MSM0969 Msp_1406 predicted metal-binding 4.9E−54 MTH_1014 conserved protein 5.6E−58 transcription factor MSM0970 Msp_0784 hypothetical protein 1.3E−21 NONE MSM0971 Msp_0393 methyl-coenzyme M reductase, 7.6E−191 NONE methyl coenzyme M 4.3E−209 component A2 reductase system, component A2 MSM0972 Msp_1405 conserved hypothetical protein 1.3E−46 MTH_1016 conserved protein 5.5E−51 MSM0973 Msp_1404 putative GTP cyclohydrolase III 9.2E−76 MTH_1017 conserved protein 1.3E−88 MSM0974 Msp_1403 CofD 3.6E−90 MTH_1018 conserved protein 8.0E−98 MSM0975 Msp_1402 CofE 3.8E−63 MTH_1019 conserved protein 1.6E−76 MSM0976 Msp_1398 PurO 2.8E−51 MTH_1020 conserved protein 1.0E−51 MSM0977 Msp_1397 conserved hypothetical 3.7E−24 MTH_1021 unknown 3.2E−30 membrane-spanning protein MSM0978 Msp_1396 predicted biopolymer transport 1.5E−77 MTH_1022 biopolymer transport 4.1E−94 protein protein MSM0979 Msp_1395 RnhB 1.6E−48 MTH_1023 ribonuclease HII 9.8E−61 MSM0980 Msp_1517 DnaK 5.3E−16 MTH_1024 rod shape-determining 7.3E−136 protein MSM0981 NONE MTH_1025 unknown 2.6E−51 MSM0982 Msp_1394 partially conserved hypothetical 2.4E−38 MTH_1027 CDP-diacylglycerol-serine 8.2E−41 membrane-spanning protein O-phosphatidyltransferase MSM0983 Msp_1393 conserved hypothetical 8.7E−48 MTH_1028 unknown 1.7E−70 membrane-spanning protein MSM0984 NONE MTH_1030 unknown 1.4E−45 MSM0985 Msp_1392 conserved hypothetical protein 1.1E−29 MTH_1031 conserved protein 6.3E−34 MSM0986 Msp_0760 putative bile salt acid hydrolase 4.3E−110 NONE MSM0987 Msp_0329 MfnA 3.9E−100 MTH_1116 glutamate decarboxylase 6.1E−123 MSM0988 Msp_0328 PpsA 1.7E−273 MTH_1118 phosphoenolpyruvate 2.0E−250 synthase MSM0989 Msp_0327 50S ribosomal protein L10e 2.8E−58 MTH_1119 ribosomal protein L10 2.1E−65 MSM0990 Msp_1000 predicted ABC-type 4.7E−40 MTH_920 anion permease 4.2E−37 nitrate/sulfonate/bicarbonate transport system, ATB-binding protein MSM0991 Msp_1001 predicted ABC-type 2.4E−11 MTH_478 sulfate transport system 4.1E−09 nitrate/sulfonate/bicarbonate permease protein transport system, permease protein MSM0992 Msp_0326 hypothetical protein 1.0E−12 MTH_1121 unknown 8.9E−12 MSM0993 Msp_0601 partially conserved hypothetical 3.9E−04 MTH_1123 unknown 1.9E−15 protein, predicted GTPase MSM0994 Msp_0324 predicted nucleotidyltransferase 3.4E−101 MTH_1126 conserved protein 2.7E−90 MSM0995 Msp_0590 member of asn/thr-rich large 8.7E−33 MTH_716 cell surface glycoprotein 1.3E−09 protein family (s-layer protein) MSM0996 Msp_0983 member of asn/thr-rich large 2.6E−26 MTH_716 cell surface glycoprotein 1.1E−09 protein family (s-layer protein) MSM0997 Msp_0323 PyrC 1.1E−97 MTH_1127 dihydroorotase 7.8E−100 MSM0998 Msp_1447 EhbK 1.0E−30 MTH_1133 polyferredoxin (MvhB) 4.4E−145 MSM0999 Msp_0316 MvhA 3.4E−181 NONE methyl viologen-reducing 2.1E−207 hydrogenase, alpha subunit MSM1000 Msp_0315 MvhG 3.2E−128 NONE methyl viologen-reducing 5.5E−138 hydrogenase, gamma subunit MSM1001 Msp_0314 MvhD1 3.9E−61 NONE methyl viologen-reducing 1.6E−67 hydrogenase, delta subunit MSM1002 Msp_0312 conserved hypothetical protein 1.2E−130 MTH_1150 ABC transporter subunit 3.5E−152 Ycf24 MSM1003 Msp_0313 predicted ABC-type transport 3.2E−82 MTH_1149 ABC transporter subunit 8.0E−98 system Ycf16 MSM1004 Msp_0311 conserved hypothetical protein 1.2E−27 MTH_1151 unknown 9.3E−33 MSM1005 Msp_0310 predicted 4.0E−36 MTH_1152 conserved protein 7.0E−35 GTP:adenosylcobinamide- phosphate guanylyltransferase MSM1006 Msp_0308 conserved hypothetical protein 2.2E−90 MTH_1153 conserved protein 5.2E−165 MSM1007 Msp_0307 MtrH 2.1E−108 MTH_1156 N5-methyl- 2.9E−125 tetrahydromethanopterin:coenzyme M methyltransferase, subunit H MSM1008 Msp_0306 MtrG 5.7E−12 MTH_1157 N5-methyl- 4.2E−21 tetrahydromethanopterin:coenzyme M methyltransferase, subunit G MSM1009 Msp_0305 MtrF 5.5E−07 MTH_1158 N5-methyl- 9.3E−17 tetrahydromethanopterin:coenzyme M methyltransferase, subunit F MSM1010 Msp_0304 MtrA 9.0E−62 MTH_1159 N5-methyl- 9.8E−93 tetrahydromethanopterin:coenzyme M methyltransferase, subunit A MSM1011 Msp_0303 MtrB 1.0E−12 MTH_1160 N5-methyl- 1.7E−31 tetrahydromethanopterin:coenzyme M methyltransferase, subunit B MSM1012 Msp_0302 MtrC 7.6E−49 MTH_1161 N5-methyl- 7.2E−81 tetrahydromethanopterin:coenzyme M methyltransferase, subunit C MSM1013 Msp_0301 MtrD 2.0E−57 MTH_1162 N5-methyl- 1.0E−81 tetrahydromethanopterin:coenzyme M methyltransferase, subunit D MSM1014 Msp_0300 MtrE 9.5E−74 MTH_1163 N5-methyl- 1.5E−121 tetrahydromethanopterin:coenzyme M methyltransferase, subunit E MSM1015 Msp_0321 MrtA 7.6E−207 NONE methyl coenzyme M 1.7E−253 reductase I, alpha subunit MSM1016 Msp_0320 MrtG 6.2E−86 NONE methyl coenzyme M 2.9E−109 reductase I, gamma subunit MSM1017 Msp_0299 McrC 2.8E−67 NONE methyl coenzyme M 2.6E−83 reductase I, C protein MSM1018 Msp_0319 MrtD 7.4E−19 NONE methyl coenzyme M 1.1E−34 reductase I, D protein MSM1019 Msp_0318 MrtB 1.6E−133 NONE methyl coenzyme M 3.4E−177 reductase I, beta subunit MSM1020 Msp_0298 predicted Fe—S oxidoreductase 2.0E−119 MTH_1170 conserved protein 1.7E−136 MSM1021 Msp_0284 conserved hypothetical protein 1.7E−99 MTH_1180 conserved protein 6.7E−117 MSM1022 Msp_0285 conserved hypothetical protein 8.5E−34 MTH_1181 unknown 2.0E−23 MSM1023 Msp_0973 ComB2 1.3E−44 MTH_1182 conserved protein 2.7E−42 MSM1024 Msp_0287 conserved hypothetical 1.9E−98 MTH_1183 pheromone shutdown 4.4E−58 membrane-spanning protein protein TraB MSM1025 Msp_0288 hypothetical protein 1.5E−20 MTH_1184 unknown 3.0E−20 MSM1026 NONE MTH_1224 inosine-5′- 5.6E−04 monophosphate dehydrogenase related protein III MSM1027 NONE MTH_1155 Na+/Ca+ exchanging 2.1E−42 protein related MSM1028 Msp_0289 predicted ATPase 9.5E−74 MTH_1186 conserved protein 2.0E−85 MSM1029 Msp_0693 conserved hypothetical protein 1.3E−39 MTH_1187 conserved protein 3.2E−23 MSM1030 Msp_0290 predicted pyridoxal phosphate- 1.3E−124 MTH_1188 pleiotropic regulatory 6.1E−123 dependent enzyme protein DegT MSM1031 Msp_0291 N2,N2-dimethylguanosine tRNA 1.1E−109 NONE N2,N2-dimethylguanosine 4.1E−110 methyltransferase tRNA methyltransferase MSM1032 Msp_0293 predicted transcriptional regulator 9.3E−44 MTH_1193 transcriptional regulator 2.9E−52 MSM1033 Msp_0294 conserved hypothetical protein 1.8E−109 MTH_1196 conserved protein 7.7E−116 MSM1034 Msp_0295 conserved hypothetical protein 6.0E−17 MTH_1197 conserved protein 1.1E−22 MSM1035 Msp_0296 CofG 4.2E−96 MTH_1198 biotin synthetase related 6.4E−105 protein MSM1036 Msp_0297 predicted methyltransferase 2.3E−70 MTH_1200 met-10+ related protein 5.7E−72 MSM1037 Msp_0282 PsmB 7.5E−58 NONE proteasome, beta subunit 7.8E−68 MSM1038 Msp_0281 predicted exonuclease 5.4E−245 MTH_1203 cleavage and 3.5E−278 polyadenylation specificity factor MSM1039 Msp_0280 PurM 1.6E−103 MTH_1204 phosphoribosylformylglycinamidine 4.0E−112 cyclo-ligase MSM1040 Msp_0279 ComC 7.6E−104 MTH_1205 malate dehydrogenase 5.7E−104 MSM1041 Msp_1507 putative DNA polymerase 6.8E−167 MTH_1208 DNA-dependent DNA 5.1E−183 polymerase family B (PolB1) MSM1042 NONE MTH_1211 conserved protein 4.0E−71 MSM1043 Msp_1420 PyrK 4.4E−69 NONE cytochrome-c3 1.6E−74 hydrogenase, gamma subunit MSM1044 Msp_1421 PyrD 7.4E−90 MTH_1213 dihydroorotate oxidase 1.3E−106 MSM1045 Msp_0220 predicted glycosyltransferase 1.9E−12 MTH_1626 phosphoserine 2.4E−05 phosphatase MSM1046 Msp_1422 predicted ribosomal biogenesis 1.2E−89 MTH_1214 pre-mRNA splicing protein 1.4E−88 protein PRP31 MSM1047 Msp_1423 FlpA 5.3E−64 MTH_1215 fibrillarin-like pre-rRNA 2.5E−62 processing protein MSM1048 Msp_1424 predicted 1.9E−43 MTH_1216 pantothenate metabolism 2.3E−52 phosphopantothenoylcysteine flavoprotein synthetase/decarboxylase MSM1049 Msp_1424 predicted 2.0E−55 MTH_1216 pantothenate metabolism 2.2E−54 phosphopantothenoylcysteine flavoprotein synthetase/decarboxylase MSM1050 Msp_1425 conserved hypothetical 4.7E−11 MTH_1218 unknown 3.3E−21 membrane-spanning protein MSM1051 Msp_1426 hypothetical membrane-spanning 3.5E−05 MTH_1219 unknown 9.0E−19 protein MSM1052 Msp_1427 PheA 2.5E−59 MTH_1220 chorismate mutase 1.1E−70 MSM1053 Msp_1428 conserved hypothetical protein 4.4E−60 MTH_1222 inosine-5′- 4.5E−72 monophosphate dehydrogenase related protein I MSM1054 Msp_1429 conserved hypothetical protein 2.2E−74 MTH_1224 inosine-5′- 1.3E−83 monophosphate dehydrogenase related protein III MSM1055 Msp_1431 partially conserved hypothetical 1.9E−36 MTH_1227 coenzyme PQQ synthesis 1.9E−57 protein protein III MSM1056 Msp_1432 putative 6-pyruvoyl 1.4E−38 MTH_1228 conserved protein 4.6E−47 tetrahydrobiopterin synthase MSM1057 Msp_1433 conserved hypothetical protein 2.1E−53 MTH_1229 conserved protein 2.1E−49 MSM1058 Msp_1434 conserved hypothetical protein 5.6E−85 MTH_1231 conserved protein 1.1E−95 MSM1059 Msp_0945 predicted RecB family 1.2E−06 MTH_1233 unknown 1.4E−36 exonuclease MSM1060 Msp_1436 EhbQ 4.9E−61 MTH_1235 conserved protein 1.2E−69 MSM1061 Msp_1442 EhbP 6.3E−22 MTH_1236 conserved protein 1.6E−28 MSM1062 Msp_1443 EhbO 6.1E−79 NONE NADH dehydrogenase 5.8E−111 (ubiquinone), subunit 1 related protein MSM1063 Msp_1444 EhbN 8.0E−141 NONE formate hydrogenlyase, 2.8E−143 subunit 5 MSM1064 Msp_1445 EhbM 1.0E−62 NONE formate hydrogenlyase, 1.6E−67 subunit 7 MSM1065 Msp_1446 EhbL 8.6E−41 MTH_1240 ferredoxin-like protein 3.4E−51 MSM1066 Msp_1447 EhbK 7.7E−72 MTH_1241 polyferredoxin 1.7E−97 MSM1067 Msp_1448 EhbJ 4.5E−12 MTH_1242 unknown 5.5E−19 MSM1068 Msp_1449 EhbI 4.2E−48 MTH_1243 conserved protein 1.0E−49 MSM1069 Msp_1450 EhbH 3.5E−21 MTH_1244 conserved protein 5.0E−25 MSM1070 Msp_1451 EhbG 4.8E−15 MTH_1245 unknown 6.6E−16 MSM1071 Msp_1452 EhbF 1.1E−134 NONE NADH dehydrogenase I, 8.4E−142 subunit N MSM1072 Msp_1453 EhbE 2.0E−32 MTH_1247 conserved protein 4.5E−40 MSM1073 Msp_1454 EhbD 4.1E−18 MTH_1248 conserved protein 9.4E−24 MSM1074 Msp_1455 EhbC 1.4E−10 MTH_1249 conserved protein 1.5E−18 MSM1075 Msp_1456 EhbB 2.2E−10 MTH_1250 unknown 1.1E−13 MSM1076 Msp_1457 EhbA 1.2E−27 MTH_1251 conserved protein 6.8E−37 MSM1077 Msp_1336 predicted permease 2.3E−05 NONE MSM1078 Msp_1336 predicted permease 9.6E−97 MTH_900 conserved protein 3.1E−32 MSM1079 Msp_1458 conserved hypothetical 2.1E−28 MTH_1252 conserved protein 1.6E−35 membrane-spanning protein MSM1080 NONE MTH_1253 unknown 2.5E−48 MSM1081 Msp_0795 partially conserved hypothetical 1.4E−56 MTH_1634 transcriptional control 5.0E−176 protein factor (enhancer-binding protein) MSM1082 NONE NONE MSM1083 Msp_0202 conserved hypothetical 4.5E−35 MTH_230 unknown 1.0E−33 membrane-spanning protein MSM1084 Msp_1459 ArgG 7.4E−138 MTH_1254 argininosuccinate 2.1E−136 synthase MSM1085 Msp_1240 AqpM2 1.8E−54 MTH_103 water channel protein 1.5E−71 MSM1086 NONE MTH_101 unknown 3.8E−194 MSM1087 NONE NONE MSM1088 NONE NONE MSM1089 Msp_0506 hypothetical membrane-spanning 3.3E−04 NONE protein MSM1090 Msp_1057 SfsA 6.0E−33 MTH_1521 sugar fermentation 3.6E−31 stimulation protein MSM1091 Msp_1501 predicted sugar kinase 3.6E−97 MTH_1256 conserved protein 1.4E−114 MSM1092 Msp_1502 formylmethanofuran- 1.2E−91 MTH_1259 formylmethanofuran: 1.3E−127 tetrahydromethanopterin tetrahydromethanopterin formyltransferase formyltransferase MSM1093 Msp_0233 conserved hypothetical protein 2.3E−22 NONE MSM1094 Msp_1503 conserved hypothetical 2.8E−81 MTH_1261 conserved protein 7.2E−97 membrane-spanning protein MSM1095 Msp_0830 Trk-type potassium transport 2.6E−62 MTH_1264 TRK system potassium 2.1E−122 system, membrane protein uptake protein TrkH MSM1096 Msp_0250 TrkA1 3.1E−52 MTH_1265 TRK system potassium 3.6E−79 uptake protein TrkA MSM1097 Msp_1505 putative Zn-dependent hydrolase 2.3E−40 MTH_1267 conserved protein 1.2E−53 MSM1098 Msp_1418 putative archaeal holliday junction 1.4E−38 MTH_1270 conserved protein 1.4E−43 resolvase MSM1099 Msp_0270 predicted biotin synthase related 7.4E−106 MTH_1279 conserved protein 2.3E−75 protein MSM1100 NONE MTH_627 unknown 7.2E−10 MSM1101 Msp_0269 GatB 1.4E−175 MTH_1280 PET112-like protein 3.6E−182 MSM1102 Msp_0268 conserved hypothetical protein 3.4E−78 MTH_1282 inosine-5′- 2.3E−93 monophosphate dehydrogenase related protein VI MSM1103 Msp_0267 HisE 4.8E−31 MTH_1283 phosphoribosyl-AMP 3.0E−34 cyclohydrolase homolog MSM1104 Msp_1506 predicted acetyltransferase 2.6E−11 MTH_1284 conserved protein 3.2E−16 MSM1105 Msp_1492 conserved hypothetical protein 7.0E−62 MTH_1286 phosphoribosylaminoimidazole 1.7E−65 carboxylase related protein MSM1106 Msp_1497 HypF 8.5E−208 MTH_1287 transcriptional regulator 2.3E−219 HypF homolog MSM1107 Msp_1519 predicted transcriptional regulator 6.6E−34 MTH_1288 unknown 1.8E−52 MSM1108 Msp_1518 GrpE 2.1E−44 MTH_1289 heat shock protein GrpE 1.6E−44 MSM1109 Msp_1517 DnaK 8.6E−247 MTH_1290 DnaK protein (Hsp70) 7.7E−251 MSM1110 Msp_1516 DnaJ 3.0E−118 MTH_1291 DnaJ protein 1.0E−122 MSM1111 Msp_0145 member of asn/thr-rich large 5.9E−49 MTH_716 cell surface glycoprotein 7.7E−12 protein family (s-layer protein) MSM1112 Msp_0762 member of asn/thr-rich large 1.6E−40 MTH_716 cell surface glycoprotein 3.3E−11 protein family (s-layer protein) MSM1113 Msp_0762 member of asn/thr-rich large 2.9E−70 MTH_716 cell surface glycoprotein 1.2E−05 protein family (s-layer protein) MSM1114 Msp_0145 member of asn/thr-rich large 1.3E−24 MTH_716 cell surface glycoprotein 3.3E−15 protein family (s-layer protein) MSM1115 Msp_0017 conserved hypothetical protein 2.2E−21 NONE MSM1116 Msp_1108 member of asn/thr-rich large 4.2E−137 MTH_911 probable surface protein 1.5E−12 protein family MSM1117 Msp_1110 CobN 8.5E−304 MTH_514 cobalamin biosynthesis 1.4E−239 protein N MSM1118 Msp_1494 hypothetical membrane-spanning 1.5E−18 MTH_1294 unknown 2.5E−23 protein MSM1119 Msp_1495 hypothetical membrane-spanning 4.1E−25 MTH_1295 unknown 4.8E−36 protein MSM1120 Msp_1496 methionine aminopeptidase 3.4E−53 MTH_1296 methionine 2.8E−86 aminopeptidase MSM1121 Msp_1305 FrhB 3.9E−77 NONE coenzyme F420-reducing 2.1E−97 hydrogenase, beta subunit MSM1122 Msp_1304 FrhG 4.6E−81 NONE coenzyme F420-reducing 2.2E−102 hydrogenase, gamma subunit MSM1123 Msp_1514 putative coenzyme F420 9.3E−44 NONE coenzyme F420-reducing 4.7E−61 hydrogenase, delta subunit-like hydrogenase, delta protein subunit MSM1124 Msp_1302 FrhA 9.4E−138 NONE coenzyme F420-reducing 8.8E−163 hydrogenase, alpha subunit MSM1125 Msp_1110 CobN 2.3E−10 MTH_1301 unknown 3.8E−11 MSM1126 Msp_0120 predicted transcriptional regulator 3.1E−20 MTH_1795 transcriptional regulator 1.1E−20 MSM1127 Msp_0121 predicted cation transport ATPase 1.2E−162 MTH_411 cadmium efflux ATPase 1.2E−119 MSM1128 NONE NONE MSM1129 Msp_1523 conserved hypothetical protein 2.3E−118 MTH_1305 conserved protein 3.6E−134 MSM1130 Msp_1028 conserved hypothetical protein 4.5E−44 MTH_1868 conserved protein 1.4E−15 MSM1131 Msp_1524 conserved hypothetical protein 1.1E−56 MTH_1306 conserved protein 1.1E−59 MSM1132 Msp_1525 ribosome biogenesis protein 2.3E−15 MTH_1307 unknown 4.0E−16 Nop10 MSM1133 Msp_1527 putative translation initiation factor 3.4E−94 NONE translation initiation factor 3.5E−104 2, alpha subunit (alF-2alpha) elF-2, alpha subunit (elF2A) MSM1134 Msp_1528 30S ribosomal protein S27e 2.3E−17 MTH_1309 ribosomal protein S27 8.1E−18 MSM1135 Msp_1529 50S ribosomal protein L44e 1.6E−41 MTH_1310 ribosomal protein L36a 2.7E−42 MSM1136 Msp_1530 partially conserved hypothetical 1.6E−30 MTH_1311 unknown 2.1E−49 protein MSM1137 Msp_1531 DNA polymerase sliding clamp 1.5E−73 MTH_1312 proliferating-cell nuclear 6.0E−93 (PCNA) antigen MSM1138 Msp_0580 predicted glutamine 5.2E−73 MTH_787 cobyric acid synthase 9.2E−10 amidotransferase MSM1139 Msp_0581 predicted UDP-N-acetylmuramyl 3.6E−90 MTH_530 UDP-N-acetylmuramyl 6.8E−16 tripeptide synthase tripeptide synthetase related protein MSM1140 Msp_0417 hypothetical membrane-spanning 2.7E−04 NONE protein MSM1141 Msp_1075 TrpA 7.3E−44 NONE tryptophan synthase, 6.5E−48 subunit alpha MSM1142 Msp_1074 TrpB 6.4E−123 NONE tryptophan synthase, 1.3E−120 beta subunit MSM1143 Msp_1072 TrpC 1.7E−42 MTH_1657 indole-3-glycerol 1.4E−38 phosphate synthase MSM1144 Msp_1076 TrpD 2.0E−71 MTH_1661 anthranilate 2.3E−68 phosphoribosyltransferase MSM1145 Msp_1071 TrpG 7.4E−51 MTH_1656 anthranilate synthase 1.1E−43 component II MSM1146 Msp_1070 TrpE 6.5E−78 MTH_1655 anthranilate synthase 9.9E−84 component I MSM1147 NONE NONE MSM1148 NONE MTH_1189 conserved protein 8.2E−08 MSM1149 Msp_0607 hypothetical membrane-spanning 6.0E−33 MTH_1192 conserved protein 2.8E−31 protein MSM1150 Msp_0608 predicted transcriptional regulator 9.4E−19 MTH_1328 conserved protein 1.3E−17 MSM1151 Msp_1247 PurB 6.0E−159 MTH_1537 adenylosuccinate lyase 8.4E−174 MSM1152 Msp_0879 hypothetical membrane-spanning 2.8E−04 MTH_1538 unknown 6.4E−25 protein MSM1153 Msp_0224 predicted cation transport ATPase 1.1E−205 MTH_1535 heavy-metal transporting 5.1E−199 CPx-type ATPase MSM1154 Msp_0200 predicted metal-dependent 1.2E−07 MTH_1534 aryldialkylphosphatase 5.0E−89 hydrolase related protein MSM1155 Msp_0225 conserved hypothetical protein 1.4E−40 MTH_1530 conserved protein 1.7E−42 MSM1156 Msp_0221 TruD 6.2E−125 MTH_1529 conserved protein 4.6E−134 MSM1157 Msp_1512 hypothetical membrane-spanning 3.5E−05 MTH_1526 conserved protein 8.9E−04 protein MSM1158 Msp_1511 HypE2 8.9E−126 MTH_1525 hydrogenase 4.2E−156 expression/formation protein HypE related protein MSM1159 Msp_1510 HisH 3.0E−38 MTH_1524 imidazoleglycerol- 9.1E−58 phosphate synthase MSM1160 Msp_1461 predicted nitrogenase 3.8E−118 MTH_1522 nitrogenase alpha chain 8.9E−131 molybdenum-iron protein (NifD) related protein MSM1161 Msp_0719 partially conserved hypothetical 2.8E−05 NONE membrane-spanning protein MSM1162 NONE NONE MSM1163 NONE NONE MSM1164 Msp_1463 predicted GTPase 1.4E−143 MTH_1515 GTP-binding protein 2.4E−153 MSM1165 Msp_1472 predicted phosphohydrolase 2.2E−67 MTH_1179 conserved protein 9.0E−10 MSM1166 Msp_1474 conserved hypothetical membrane- 1.5E−146 NONE spanning protein MSM1167 Msp_1464 CbiE 6.8E−48 MTH_1514 precorrin-6Y methylase 3.9E−50 MSM1168 Msp_0590 member of asn/thr-rich large 1.7E−16 MTH_75 surface protease related 2.1E−11 protein family protein MSM1169 NONE NONE MSM1170 Msp_0169 putative arsenical prump-driving 5.3E−96 MTH_1511 arsenical pump-driving 6.9E−108 ATPase ATPase MSM1171 Msp_0170 NadE 1.1E−63 MTH_1510 NH(3)-dependent NAD+ 1.3E−60 synthetase MSM1172 Msp_0171 LeuS 0.0E+00 MTH_1508 leucyl-tRNA synthetase 0.0E+00 MSM1173 Msp_0004 predicted tRNA(1- 1.0E−62 MTH_1414 protein-L-isoaspartate 1.4E−77 methyladenosine) methyltransferase methyltransferase homolog MSM1174 Msp_0309 HtpX 1.8E−38 MTH_569 heat shock protein X 2.1E−67 MSM1175 Msp_0548 hypothetical membrane-spanning 6.6E−11 NONE protein MSM1176 Msp_0413 RfcS 2.2E−115 NONE replication factor C, small 3.7E−125 subunit MSM1177 Msp_0414 RfcL 1.1E−113 NONE replication factor C, large 3.8E−123 subunit MSM1178 Msp_0578 conserved hypothetical protein 4.1E−34 MTH_239 unknown 9.7E−38 MSM1179 Msp_0647 AroE 1.8E−72 MTH_242 shikimate 5- 1.2E−71 dehydrogenase MSM1180 NONE MTH_1189 conserved protein 1.6E−08 MSM1181 Msp_0648 HisS 5.1E−114 MTH_244 histidyl-tRNA synthetase 3.8E−130 MSM1182 Msp_0649 HisI 1.6E−39 MTH_245 phosphoribosyl-AMP 1.0E−40 cyclohydrolase MSM1183 Msp_0650 predicted ATPase 1.5E−155 MTH_246 twitching mobility (PilT) 8.0E−185 related protein MSM1184 Msp_0651 predicted sugar phosphate 8.7E−48 MTH_247 conserved protein 4.5E−49 isomerase/epimerase or endonuclease MSM1185 Msp_1499 putative methylated-DNA-protein- 1.3E−12 MTH_618 O6-methylguanidine- 2.8E−15 cysteine methyltransferase DNA methyltransferase MSM1186 Msp_1489 predicted potassium transport 9.9E−111 NONE system, membrane component MSM1187 Msp_0007 predicted ERCC4-like helicase 5.4E−213 NONE ATP-dependent RNA 3.5E−241 helicase, elF-4A family MSM1188 Msp_0590 member of asn/thr-rich large 1.4E−49 MTH_716 cell surface glycoprotein 6.9E−13 protein family (s-layer protein) MSM1189 Msp_0017 conserved hypothetical protein 1.7E−28 NONE MSM1190 Msp_1211 partially conserved hypothetical 6.7E−128 MTH_530 UDP-N-acetylmuramyl 3.1E−57 membrane-spanning protein tripeptide synthetase related protein MSM1191 Msp_1212 predicted UDP-N- 7.9E−102 MTH_531 UDP-N-acetylmuramyl 1.3E−40 acetylmuramoylalanine-D- tripeptide synthetase glutamate ligase related protein MSM1192 Msp_0008 conserved hypothetical protein 9.1E−124 MTH_1421 conserved protein 5.0E−137 MSM1193 Msp_0009 putative single-stranded-DNA- 9.9E−111 MTH_1422 conserved protein 9.3E−136 specific exonuclease MSM1194 Msp_0010 30S ribosomal protein S15P 5.3E−48 MTH_1423 ribosomal protein S13 2.1E−49 (E. coli) MSM1195 Msp_0011 putative xanthosine triphosphate 1.9E−61 MTH_1424 conserved protein 1.2E−62 pyrophosphatase MSM1196 Msp_0635 cell division control protein 6-like 2 9.7E−06 NONE MSM1197 NONE NONE MSM1198 Msp_0013 putative O-sialoglycoprotein 7.7E−159 MTH_1425 O-sialoglycoprotein 1.9E−174 endopeptidase endopeptidase MSM1199 Msp_0999 hypothetical protein 7.0E−06 NONE MSM1200 Msp_0012 predicted 1.4E−88 MTH_1426 conserved protein 3.4E−99 phosphoribosyltransferase MSM1201 Msp_0014 UppP 6.0E−72 MTH_1428 bacitracin resistance 1.1E−43 protein MSM1202 Msp_0015 IlvE 4.0E−114 MTH_1430 branched-chain amino- 5.2E−110 acid aminotransferase MSM1203 Msp_0724 hypothetical membrane-spanning 6.7E−09 MTH_470 conserved protein 7.9E−05 protein MSM1204 Msp_0163 F420-dependent 4.0E−82 NONE coenzyme F420- 2.2E−102 methylenetetrahydromethanopterin dependent N5,N10- dehydrogenase methylene tetrahydromethanopterin dehydrogenase MSM1205 Msp_0417 hypothetical membrane-spanning 5.3E−04 MTH_1490 unknown 3.5E−17 protein MSM1206 Msp_0164 HisB 2.5E−57 MTH_1467 imidazoleglycerol- 9.7E−54 phosphate dehydratase MSM1207 NONE MTH_1470 molybdenum transport 2.2E−17 protein ModA related protein MSM1208 Msp_0165 predicted polysaccharide 5.0E−116 MTH_1471 O-antigen transporter 3.2E−87 biosynthesis protein homolog MSM1209 Msp_0540 predicted multimeric flavodoxin 6.7E−25 MTH_1473 conserved protein 4.7E−54 MSM1210 Msp_0925 predicted arabinose efflux 7.5E−22 MTH_195 efflux pump antibiotic 2.5E−24 permease resistance protein MSM1211 Msp_0260 hypothetical protein 4.6E−16 MTH_1626 phosphoserine 4.3E−06 phosphatase MSM1212 NONE NONE MSM1213 Msp_1498 formaldehyde activating enzyme 8.3E−162 MTH_1474 D-arabino 3-hexulose 6- 6.3E−169 fused to 3-hexulose-6phosphate phosphate formaldehyde synthase lyase related protein MSM1214 Msp_1573 ThrS 7.3E−202 MTH_1455 threonyl-tRNA 1.3E−225 synthetase MSM1215 Msp_0162 CbiA 1.7E−147 NONE cobyrinic acid a,c- 9.4E−143 diamide synthase MSM1216 Msp_0166 conserved hypothetical membrane- 1.3E−74 MTH_1461 conserved protein 2.1E−67 spanning protein MSM1217 Msp_0019 partially conserved hypothetical 5.0E−45 MTH_1434 unknown 1.3E−55 protein MSM1218 Msp_0020 SurE 1.2E−68 MTH_1435 survival protein SurE 1.5E−73 MSM1219 NONE NONE MSM1220 NONE MTH_1440 unknown 8.6E−14 MSM1221 Msp_0021 conserved hypothetical protein 5.2E−89 MTH_1441 conserved protein 3.4E−106 MSM1222 Msp_0022 IlvC 6.9E−126 MTH_1442 ketol-acid 2.7E−122 reductoisomerase MSM1223 Msp_0591 predicted carbonic anhydrase 8.1E−13 MTH_1582 carbonic anhydrase 3.7E−38 MSM1224 Msp_0025 IlvH1 1.1E−45 NONE acetolactate synthase, 4.1E−55 small subunit MSM1225 Msp_0026 IlvB1 6.3E−180 NONE acetolactate synthase, 3.5E−207 large subunit MSM1226 Msp_0031 ArgF 2.3E−102 MTH_1446 ornithine 4.6E−102 carbamoyltransferase MSM1227 Msp_0030 PurD 1.1E−150 MTH_1445 glycinamide 4.2E−147 ribonucleotide synthetase MSM1228 Msp_0513 predicted Na+-driven multidrug 5.6E−108 MTH_314 conserved protein 2.8E−95 efflux pump MSM1229 Msp_0513 predicted Na+-driven multidrug 1.1E−125 MTH_314 conserved protein 3.1E−105 efflux pump MSM1230 Msp_0512 predicted transcriptional regulator 5.3E−25 MTH_313 transcriptional regulator 2.2E−17 MSM1231 Msp_1574 ArgS 1.4E−157 MTH_1447 arginyl-tRNA synthetase 9.3E−175 MSM1232 Msp_1575 putative signal peptidase 3.6E−42 MTH_1448 signal peptidase 2.7E−42 MSM1233 Msp_1180 HemL 5.8E−138 MTH_228 glutamate-1- 2.1E−136 semialdehyde aminotransferase MSM1234 Msp_1179 CbiC 8.2E−68 MTH_227 precorrin isomerase 7.1E−58 MSM1235 Msp_0093 predicted flavoprotein 2.5E−59 NONE MSM1236 Msp_0135 AspS 1.9E−164 MTH_226 aspartyl-tRNA 1.2E−165 synthetase MSM1237 Msp_1576 IlvD 7.2E−195 MTH_1449 dihydroxy-acid 3.4E−177 dehydratase MSM1238 Msp_0134 HisD 2.7E−131 MTH_225 histidinol dehydrogenase 2.7E−138 MSM1239 Msp_1569 predicted DNA-binding protein 2.7E−92 MTH_1458 unknown 5.1E−96 MSM1240 Msp_1570 conserved hypothetical protein 8.9E−23 MTH_1457 unknown 3.0E−24 MSM1241 Msp_1571 predicted ATPase 5.2E−82 MTH_1456 chromosome partitioning 1.9E−73 protein Soj MSM1242 Msp_1074 TrpB 7.2E−37 NONE tryptophan synthase, 1.0E−168 beta subunit homolog MSM1243 NONE MTH_1477 unknown 3.1E−73 MSM1244 Msp_1491 predicted metal-dependent 1.9E−45 MTH_1478 conserved protein 8.9E−28 phosphoesterase MSM1245 Msp_0198 AlbA 2.2E−26 MTH_1483 conserved protein 3.8E−27 MSM1246 Msp_0199 LeuA1 8.3E−162 MTH_1481 isopropylmalate synthase 2.8E−175 MSM1247 Msp_0197 conserved hypothetical membrane- 2.6E−78 MTH_1485 serine/threonine protein 1.2E−92 spanning protein kinase related protein MSM1248 Msp_0196 ABC-type multidrug transport 4.6E−74 MTH_1486 conserved protein 1.5E−82 system, permease protein MSM1249 Msp_0195 ABC-type multidrug transport 1.6E−94 MTH_1487 ABC transporter (ATP- 5.1E−103 system, ATP-binding protein binding MSM1250 Msp_0194 predicted transcriptional regulator 3.6E−19 MTH_1488 unknown 1.6E−19 MSM1251 Msp_0651 predicted sugar phosphate 7.5E−26 MTH_1489 conserved protein 8.8E−60 isomerase/epimerase or endonuclease MSM1252 Msp_0191 MapB 8.0E−38 MTH_1493 cation transporting P- 1.8E−54 type ATPase related protein MSM1253 Msp_0181 GatA 2.1E−165 MTH_1496 amidase 1.1E−164 MSM1254 Msp_0174 predicted cobyric acid synthase 7.3E−115 NONE cobyrinic acid a,c- 8.9E−115 diamide synthase related protein MSM1255 NONE NONE MSM1256 Msp_0175 RibB 2.5E−59 MTH_1499 GTP cyclohydrolase II 2.8E−63 MSM1257 Msp_0177 predicted transcriptional regulator 1.7E−19 MTH_1500 conserved protein 9.4E−24 MSM1258 Msp_0180 TfrA 2.0E−174 NONE succinate 3.9E−185 dehydrogenase, flavoprotein subunit MSM1259 Msp_0200 predicted metal-dependent 1.0E−115 MTH_1505 N-ethylammeline 9.3E−120 hydrolase chlorohydrolase homolog MSM1260 Msp_0383 archaeal histone 8.8E−16 MTH_1696 histone HMtA2 8.4E−16 MSM1261 Msp_0178 HisG 1.4E−88 MTH_1506 ATP 1.3E−90 phosphoribosyltransferase MSM1262 NONE NONE MSM1263 Msp_0003 PyrB 8.4E−98 MTH_1413 aspartate 5.1E−96 carbamoyltransferase MSM1264 Msp_0001 cell division control protein 6-like 1 4.9E−141 MTH_1412 Cdc6 related protein 8.2E−160 MSM1265 NONE MTH_1410 unknown 1.4E−31 MSM1266 Msp_1588 CobD 4.4E−76 MTH_1409 cobalamin biosynthesis 7.6E−54 protein B MSM1267 Msp_1587 CbiG 2.3E−70 MTH_1408 cobalamin biosynthesis 3.0E−50 protein G MSM1268 Msp_1586 conserved hypothetical protein 2.7E−21 MTH_1407 conserved protein 2.6E−28 MSM1269 NONE NONE MSM1270 Msp_1585 predicted class II aldolase 4.7E−40 MTH_1406 fuculose-1-phosphate 4.9E−43 aldolase MSM1271 Msp_1584 PolB 4.5E−131 MTH_1405 DNA polymerase delta 3.6E−156 small subunit MSM1272 Msp_1583 hypothetical membrane-spanning 5.8E−19 MTH_1404 unknown 4.3E−28 protein MSM1273 Msp_1582 CbiH 2.5E−98 MTH_1403 precorrin-3 methylase 1.2E−101 MSM1274 NONE MTH_1402 conserved protein 6.4E−73 MSM1275 Msp_0962 hypothetical membrane-spanning 2.4E−04 MTH_1401 unknown 5.4E−108 protein MSM1276 Msp_1558 hypothetical protein 1.7E−10 MTH_1400 unknown 1.3E−16 MSM1277 Msp_1559 conserved hypothetical membrane- 8.0E−38 MTH_1399 unknown 2.0E−46 spanning protein MSM1278 Msp_0757 predicted ATPase 4.3E−101 NONE MSM1279 Msp_1562 conserved hypothetical protein 1.5E−50 MTH_1398 conserved protein 2.3E−52 MSM1280 Msp_1561 conserved hypothetical protein 5.0E−52 MTH_1397 conserved protein 1.2E−25 MSM1281 Msp_1563 CbiX 7.5E−42 MTH_1397 conserved protein 8.6E−30 MSM1282 Msp_0590 member of asn/thr-rich large 3.1E−13 MTH_716 cell surface glycoprotein 2.7E−05 protein family (s-layer protein) MSM1283 Msp_1564 ThiL 6.8E−48 MTH_1396 thiamine monphosphate 3.1E−57 kinase MSM1284 Msp_1565 predicted pyruvate-formate lyase- 1.5E−66 MTH_1395 pyruvate formate-lyase 3.5E−81 activating enzyme activating enzyme related protein MSM1285 Msp_0615 partially conserved hypothetical 6.8E−05 NONE membrane-spanning protein MSM1286 Msp_1479 predicted 3-octaprenyl-4- 5.7E−147 MTH_1394 conserved protein 3.5E−152 hydroxybenzoate carboxy-lyase MSM1287 Msp_1480 PurE 6.4E−68 MTH_1393 phosphoribosylaminoimidazole 1.9E−80 carboxylase MSM1288 NONE NONE MSM1289 Msp_1168 CobS 6.5E−04 NONE MSM1290 Msp_0054 predicted glycosyltransferase 1.4E−33 MTH_374 dolichyl-phosphate 7.5E−31 mannose synthase related protein MSM1291 NONE NONE MSM1292 Msp_0920 predicted transcriptional accessory 9.5E−232 NONE translation initiation 2.1E−04 protein factor elF-2, alpha subunit MSM1293 Msp_0965 predicted nitroreductase 3.3E−16 MTH_120 NADPH-oxidoreductase 2.1E−33 MSM1294 Msp_1481 conserved hypothetical membrane- 3.4E−124 MTH_1392 dolichyl-phosphate 5.8E−150 spanning protein mannoosyltransferase related protein MSM1295 Msp_1482 conserved hypothetical membrane- 7.0E−94 MTH_1391 conserved protein 3.8E−114 spanning protein MSM1296 Msp_1483 RibH 2.0E−50 MTH_1390 riboflavin synthase beta 1.4E−54 subunit MSM1297 Msp_0219 conserved hypothetical protein 3.0E−70 NONE MSM1298 Msp_1484 LeuB 3.8E−109 MTH_1388 3-isopropylmalate 3.2E−103 dehydrogenase MSM1299 Msp_1485 LeuD1 3.1E−43 NONE 3-isopropylmalate 3.3E−60 dehydratase, LeuC subunit MSM1300 Msp_1486 LeuC1 1.3E−165 NONE 3-isopropylmalate 1.7E−175 dehydratase, LeuD subunit MSM1301 NONE NONE MSM1302 NONE NONE MSM1303 Msp_0214 predicted UDP-N-acetyl-D- 2.3E−143 MTH_836 UDP-N-acetyl-D- 2.8E−79 mannosaminuronate mannosaminuronic acid dehydrogenase dehydrogenase MSM1304 Msp_1116 predicted dTDP-4- 9.6E−42 MTH_1792 dTDP-4- 1.9E−73 dehydrorhamnose reductase dehydrorhamnose reductase MSM1305 Msp_0762 member of asn/thr-rich large 5.3E−36 MTH_716 cell surface glycoprotein 2.2E−12 protein family (s-layer protein) MSM1306 Msp_0590 member of asn/thr-rich large 3.5E−45 MTH_716 cell surface glycoprotein 1.8E−07 protein family (s-layer protein) MSM1307 Msp_1102 predicted dTDP-glucose 4.1E−41 MTH_1791 glucose-1-phosphate 1.4E−123 pyrophosphorylase thymidylyltransferase MSM1308 Msp_0539 predicted dTDP-4- 1.9E−68 NONE dTDP-4- 5.4E−60 dehydrorhamnose 3,5-epimerase dehydrorhamnose 3,5- epimerase MSM1309 Msp_1114 predicted dTDP-D-glucose 4,6- 4.5E−106 NONE dTDP-glucose 4,6- 3.0E−137 dehydratase dehydratase MSM1310 Msp_0212 predicted glycosyltransferase 1.8E−54 MTH_884 teichoic acid biosynthesis 7.1E−10 related protein MSM1311 Msp_0496 predicted glycosyltransferase 2.8E−34 MTH_136 dolichyl-phosphate 2.2E−05 mannose synthase MSM1312 Msp_0500 predicted glycosyltransferase 4.8E−79 MTH_172 conserved protein 6.5E−19 MSM1313 Msp_0492 predicted glycosyltransferase 6.1E−57 MTH_338 LPS biosynthesis RfbU 2.9E−07 related protein MSM1314 NONE NONE MSM1315 NONE NONE MSM1316 Msp_0495 predicted glycosyltransferase 2.3E−33 MTH_884 teichoic acid biosynthesis 8.9E−09 related protein MSM1317 Msp_0500 predicted glycosyltransferase 2.9E−07 NONE MSM1318 Msp_0927 hypothetical protein 2.1E−30 NONE MSM1319 Msp_0928 hypothetical protein 3.0E−31 NONE MSM1320 Msp_0492 predicted glycosyltransferase 4.1E−58 NONE MSM1321 Msp_0500 predicted glycosyltransferase 4.4E−76 MTH_172 conserved protein 9.5E−17 MSM1322 Msp_0492 predicted glycosyltransferase 6.5E−62 MTH_338 LPS biosynthesis RfbU 9.6E−12 related protein MSM1323 Msp_0495 predicted glycosyltransferase 5.3E−34 MTH_884 teichoic acid biosynthesis 2.0E−08 related protein MSM1324 Msp_0215 predicted glycosyltransferase 1.0E−32 MTH_884 teichoic acid biosynthesis 1.5E−08 related protein MSM1325 Msp_0204 predicted ABC-type 1.2E−64 MTH_1092 putative membrane 6.6E−06 polysaccharide/polyol phosphate protein export system, permease protein MSM1326 Msp_0205 predicted ABC-type 3.7E−79 MTH_1370 ABC transporter (ATP- 2.0E−16 polysaccharide/polyol phosphate binding protein) export system, ATP-binding protein MSM1327 NONE MTH_361 teichoic acid biosynthesis 2.4E−17 protein RodC related protein MSM1328 Msp_0212 predicted glycosyltransferase 2.9E−26 MTH_884 teichoic acid biosynthesis 2.0E−12 related protein MSM1329 Msp_0206 predicted glycosyltransferase 5.2E−82 MTH_172 conserved protein 2.5E−46 MSM1330 Msp_0207 predicted glycosyltransferase 9.1E−69 MTH_172 conserved protein 1.1E−20 MSM1331 Msp_0208 predicted bacterial sugar 9.0E−117 NONE transferase MSM1332 Msp_1487 predicted ssDNA-binding protein 6.2E−157 MTH_1385 replication factor A 7.8E−152 related protein MSM1333 Msp_1488 RadA 6.9E−142 MTH_1383 DNA repair protein RadA 6.4E−144 MSM1334 Msp_1477 predicted permease 1.4E−56 MTH_1382 conserved protein 1.2E−57 MSM1335 NONE NONE MSM1336 Msp_1476 HdrA1 6.9E−277 NONE heterodisulfide 2.0E−298 reductase, subunit A MSM1337 Msp_1475 GlyA 5.9E−145 MTH_1380 serine 6.5E−151 hydroxymethyltransferase MSM1338 Msp_1473 predicted flavoprotein 3.4E−53 MTH_1379 conserved protein 5.0E−73 (contains ferredoxin domain) MSM1339 Msp_1471 conserved hypothetical protein 2.5E−11 MTH_1377 conserved protein 9.7E−22 MSM1340 Msp_1470 S-adenosylmethionine synthetase 2.2E−138 MTH_1376 conserved protein 3.7E−148 MSM1341 Msp_1468 IleS 0.0E+00 MTH_1375 isoleucyl-tRNA 0.0E+00 synthetase MSM1342 Msp_1467 PurL 5.9E−239 MTH_1374 phosphoribosylformylglycinamidine 4.4E−255 synthase II MSM1343 NONE MTH_1369 molybdenum cofactor 2.5E−110 biosynthesis MoeA MSM1344 Msp_1466 predicted membrane-associated 1.4E−81 MTH_1368 conserved protein 3.4E−99 Zn-dependent protease MSM1345 NONE NONE MSM1346 Msp_0822 hypothetical protein 1.6E−06 NONE MSM1347 NONE NONE MSM1348 Msp_0789 rubrerythrin 2.7E−04 MTH_1351 conserved protein 4.2E−37 MSM1349 Msp_0787 FprA 2.9E−136 MTH_1350 flavoprotein AI 2.7E−152 MSM1350 Msp_0061 conserved hypothetical protein 5.4E−32 MTH_1349 conserved protein 3.1E−48 MSM1351 Msp_0038 CbiL 1.1E−58 MTH_1348 precorrin-2 9.8E−61 methyltransferase MSM1352 Msp_0036 putative ATP-dependent helicase 1.1E−175 MTH_1347 probable ATP-dependent 3.4E−212 helicase MSM1353 Msp_1532 hypothetical membrane-spanning 1.6E−08 MTH_1313 unknown 9.0E−13 protein MSM1354 Msp_1533 RpoM1 4.7E−33 MTH_1314 transcription elongation 4.8E−36 factor TFIIS MSM1355 Msp_1534 putative ADP-ribose 4.9E−38 MTH_1315 mutator MutT protein 1.1E−34 pyrophosphatase MSM1356 Msp_1535 RpoL 2.1E−14 NONE DNA-dependent RNA 5.5E−19 polymerase, subunit L MSM1357 Msp_1536 predicted RNA-binding protein 2.6E−32 MTH_1318 conserved protein 1.6E−46 MSM1358 Msp_1537 predicted diphthamide synthase, 6.1E−95 MTH_1319 conserved protein 1.1E−109 subunit DPH2 MSM1359 Msp_1538 putative adenine 5.0E−52 MTH_1320 adenine 2.2E−54 phosphoribosyltransferase phosphoribosyltransferase MSM1360 Msp_1539 signal recognition particle, 54 kDa 2.0E−151 MTH_1321 signal recognition particle 5.8E−159 protein protein SRP54 MSM1361 Msp_1541 predicted pseudouridylate synthase 4.0E−82 MTH_1322 conserved protein 1.0E−104 MSM1362 NONE MTH_809 molybdenum cofactor 2.2E−47 biosynthesis protein MoaC MSM1363 Msp_0229 SecG 2.2E−12 NONE MSM1364 Msp_0032 HisF 1.6E−112 MTH_1343 imidazoleglycerol- 3.7E−109 phosphate synthase (cyclase) MSM1365 Msp_0034 putative 3-methyladenine DNA 2.1E−37 MTH_1342 8-oxoguanine DNA 1.1E−68 glycosylase/8-oxoguanine DNA glycosylase glycosylase MSM1366 NONE MTH_758 S-D-lactoylglutathione 7.2E−26 methylglyoxal lyase MSM1367 Msp_0035 predicted peptidyl-prolyl cis-trans 2.3E−63 MTH_1338 peptidyl-prolyl cis-trans 1.9E−57 isomerase 1 isomerase B MSM1368 Msp_0037 ArgD 6.6E−121 MTH_1337 N-acetylornithine 8.1E−121 aminotransferase MSM1369 Msp_0006 predicted NUDIX-related protein 4.5E−12 MTH_1336 mutator MutT protein 1.0E−17 homolog MSM1370 Msp_0715 conserved hypothetical membrane- 9.6E−97 NONE spanning protein MSM1371 Msp_1578 LysA 2.9E−152 MTH_1335 diaminopimelate 2.3E−155 decarboxylase MSM1372 Msp_1579 DapF 1.3E−74 MTH_1334 diaminopimelate 2.8E−86 epimerase MSM1373 Msp_1545 conserved hypothetical protein 3.2E−50 MTH_1329 methyltransferase related 4.1E−46 protein MSM1374 Msp_1544 KsgA 1.6E−62 MTH_1326 dimethyladenosine 1.3E−56 transferase MSM1375 NONE MTH_1325 conserved protein 2.9E−61 MSM1376 Msp_1543 conserved hypothetical protein 5.1E−20 MTH_1324 conserved protein 2.1E−28 MSM1377 Msp_1542 50S ribosomal protein L21e 3.3E−32 MTH_1323 ribosomal protein L21 2.7E−35 MSM1378 Msp_0981 conserved hypothetical protein 7.4E−19 NONE MSM1379 Msp_0967 putative NADP-dependent alcohol 1.4E−24 NONE dehydrogenase MSM1380 Msp_0967 putative NADP-dependent alcohol 4.6E−74 NONE dehydrogenase MSM1381 Msp_0967 putative NADP-dependent alcohol 2.2E−11 NONE dehydrogenase MSM1382 Msp_0504 conserved hypothetical membrane- 2.7E−53 NONE spanning protein MSM1383 Msp_0254 anaerobic ribonucleotide- 1.6E−307 MTH_1539 anaerobic 9.9E−306 triphosphate reductase ribonucleoside- triphosphate reductase MSM1384 Msp_0255 PolC 3.9E−290 MTH_1536 conserved protein 0.0E+00 MSM1385 Msp_0113 conserved hypothetical protein 7.7E−16 MTH_1626 phosphoserine 2.3E−09 phosphatase MSM1386 NONE NONE MSM1387 Msp_0249 LysS 4.8E−205 MTH_1542 conserved protein 2.6E−202 MSM1388 Msp_0251 ThiC2 1.0E−156 MTH_1543 thiamine biosynthesis 5.3E−172 protein MSM1389 Msp_0252 predicted ribokinase 1.3E−78 MTH_1544 ribokinase 3.8E−91 MSM1390 Msp_0248 conserved hypothetical protein 2.5E−50 MTH_1545 conserved protein 1.5E−55 MSM1391 Msp_0247 predicted sugar phosphate 1.2E−52 MTH_1546 conserved protein 1.3E−51 isomerase MSM1392 NONE NONE nitrate assimilation 4.4E−58 protein, narQ MSM1393 NONE NONE MSM1394 Msp_0355 conserved hypothetical membrane- 1.5E−04 NONE spanning protein MSM1395 Msp_0340 PstB 3.1E−27 MTH_605 ABC transporter 3.2E−30 MSM1396 NONE MTH_1345 conserved protein 4.7E−22 MSM1397 Msp_0432 member of asn/thr-rich large protein 7.3E−30 MTH_911 probable surface protein 3.0E−12 family MSM1398 Msp_0762 member of asn/thr-rich large protein 4.2E−21 MTH_716 cell surface glycoprotein 2.4E−10 family (s-layer protein) MSM1399 Msp_0911 member of asn/thr-rich large protein 5.8E−13 MTH_716 cell surface glycoprotein 4.7E−13 family (s-layer protein) MSM1400 Msp_0615 partially conserved hypothetical 5.3E−05 MTH_672 unknown 1.6E−04 membrane-spanning protein MSM1401 Msp_1106 conserved hypothetical membrane- 5.9E−42 MTH_671 unknown 1.9E−48 spanning protein MSM1402 Msp_1107 conserved hypothetical membrane- 4.2E−16 MTH_670 unknown 2.4E−11 spanning protein MSM1403 NONE NONE MSM1404 Msp_0243 FwdB 5.2E−23 NONE formate dehydrogenase, 1.9E−153 alpha subunit homolog MSM1405 Msp_0639 FdhB 5.0E−84 NONE formate dehydrogenase, 7.8E−84 beta subunit related protein FlpB MSM1406 Msp_0384 predicted Fe—S oxidoreductase 2.7E−19 MTH_1550 molybdenum cofactor 2.6E−99 biosynthesis MoaA MSM1407 Msp_0488 predicted allosteric regulator of 9.7E−04 MTH_1551 molybdopterin-guanine 2.3E−36 homoserine dehydrogenase dinucleotide biosynthesis protein B related MSM1408 Msp_0147 ferredoxin 7.5E−10 NONE tungsten 8.3E−48 formylmethanofuran dehydrogenase, subunit H MSM1409 Msp_1447 EhbK 6.0E−18 NONE tungsten 3.1E−97 formylmethanofuran dehydrogenase, subunit F MSM1410 Msp_0241 FwdG 1.8E−22 NONE tungsten 2.7E−19 formylmethanofuran dehydrogenase, subunit G MSM1411 Msp_0242 FwdD 5.4E−39 NONE tungsten 6.9E−21 formylmethanofuran dehydrogenase, subunit D MSM1412 Msp_0243 FwdB 1.6E−156 NONE tungsten 5.3E−117 formylmethanofuran dehydrogenase, subunit B MSM1413 Msp_0244 FwdA 6.4E−203 NONE tungsten 1.7E−182 formylmethanofuran dehydrogenase, subunit A MSM1414 Msp_0245 FwdC 1.9E−66 NONE tungsten 2.9E−52 formylmethanofuran dehydrogenase, subunit C MSM1415 Msp_0246 hypothetical protein 3.9E−13 MTH_1568 unknown 1.1E−08 MSM1416 Msp_0246 hypothetical protein 6.8E−09 MTH_1568 unknown 1.6E−05 MSM1417 Msp_0235 conserved hypothetical membrane- 2.9E−150 MTH_1569 conserved protein 6.5E−151 spanning protein MSM1418 Msp_0234 GlnA 3.8E−157 MTH_1570 glutamine synthetase 4.7E−164 MSM1419 Msp_0017 conserved hypothetical protein 1.7E−28 NONE MSM1420 Msp_0128 predicted helicase 5.7E−11 MTH_511 DNA helicase II 1.5E−13 MSM1421 Msp_1566 conserved hypothetical membrane- 4.4E−92 NONE spanning protein MSM1422 Msp_1568 conserved hypothetical membrane- 3.5E−67 NONE spanning protein MSM1423 Msp_0721 partially conserved hypothetical 5.9E−42 NONE protein MSM1424 Msp_0720 polyphosphate kinase 2.4E−258 NONE MSM1425 Msp_0871 30S ribosomal protein S13P 7.7E−56 MTH_34 ribosomal protein S18 2.9E−54 (E. coli) MSM1426 Msp_0870 30S ribosomal protein S4P 6.5E−59 MTH_35 ribosomal protein S9 4.4E−65 (E. coli) MSM1427 Msp_0869 30S ribosomal protein S11P 2.5E−59 MTH_36 ribosomal protein S14 2.9E−61 (E. coli) MSM1428 Msp_0868 RpoD 6.3E−61 NONE DNA-dependent RNA 9.1E−74 polymerase, subunit D MSM1429 Msp_0867 50S ribosomal protein L18e 1.1E−33 MTH_38 ribosomal protein L18 5.5E−35 (E. coli) MSM1430 Msp_0866 50S ribosomal protein L13P 1.3E−51 MTH_39 ribosomal protein S16 7.1E−58 (E. coli) MSM1431 Msp_0865 30S ribosomal protein S9P 2.9E−56 MTH_39 ribosomal protein S16 1.3E−56 (E. coli) MSM1432 Msp_0864 RpoN 9.4E−19 NONE DNA-dependent RNA 1.3E−24 polymerase, subunit N MSM1433 Msp_0863 RpoK 6.9E−16 NONE DNA-dependent RNA 2.4E−18 polymerase, subunit K MSM1434 NONE NONE MSM1435 Msp_0862 enolase 2.2E−113 MTH_43 enolase 3.0E−121 MSM1436 Msp_0861 ferredoxin 3.0E−15 MTH_1106 ferredoxin 6.2E−20 MSM1437 Msp_0860 ribosomal protein S2P 3.9E−84 MTH_44 ribosomal protein Sa 5.5E−83 (E. coli) MSM1438 Msp_0859 conserved hypothetical protein 1.9E−59 MTH_45 conserved protein 5.1E−64 MSM1439 Msp_0858 putative mevalonate kinase 2.1E−60 MTH_46 mevalonate kinase 4.6E−63 MSM1440 Msp_0857 predicted archaeal kinase 9.2E−60 MTH_47 conserved protein 3.6E−70 MSM1441 Msp_0856 isopentenyl-diphosphate delta- 6.2E−118 MTH_48 conserved protein 4.1E−117 isomerase MSM1442 Msp_0855 predicted hydrolase 8.3E−178 MTH_49 conserved protein 8.6E−188 MSM1443 Msp_0854 IdsA 1.3E−90 MTH_50 bifunctional short chain 4.1E−94 isoprenyl diphosphate synthase MSM1444 NONE NONE MSM1445 Msp_1125 predicted transcriptional regulator 1.4E−38 MTH_1454 conserved protein 2.9E−45 MSM1446 Msp_1126 putative hydroxylamine reductase 1.8E−152 MTH_1453 6Fe-6S prismane- 3.6E−173 containing protein MSM1447 Msp_0002 conserved hypothetical protein 1.1E−31 MTH_1452 unknown 2.3E−36 MSM1448 Msp_1545 conserved hypothetical protein 1.9E−08 MTH_146 precorrin-8W 1.7E−05 decarboxylase MSM1449 Msp_0219 conserved hypothetical protein 7.9E−04 MTH_83 O-linked GlcNAc 9.2E−05 transferase MSM1450 Msp_0524 predicted oxidoreductase 8.4E−25 MTH_907 conserved protein 6.8E−08 MSM1451 Msp_0039 predicted glycosyltransferase 2.2E−06 MTH_83 O-linked GlcNAc 3.2E−10 transferase MSM1452 Msp_0923 GltX 1.1E−184 MTH_51 glutamyl-tRNA 8.5E−181 synthetase MSM1453 NONE NONE MSM1454 Msp_0226 hypothetical protein 9.5E−14 NONE heterodisulfide 6.6E−06 reductase, subunit C MSM1455 Msp_0924 predicted 3.8E−166 MTH_52 aspartate 6.6E−158 aspartate/tyrosine/aromatic aminotransferase related aminotransferase protein MSM1456 NONE NONE MSM1457 NONE NONE MSM1458 NONE NONE MSM1459 Msp_0925 predicted arabinose efflux 7.3E−115 MTH_195 efflux pump antibiotic 7.7E−93 permease resistance protein MSM1460 Msp_1447 EhbK 1.8E−33 MTH_1133 polyferredoxin (MvhB) 5.8E−143 MSM1461 Msp_0638 MvhD2 1.3E−53 NONE methyl viologen-reducing 2.7E−58 hydrogenase, delta subunit homolog FlpD MSM1462 Msp_0639 FdhB 1.2E−119 NONE formate dehydrogenase, 1.9E−135 beta subunit related protein FlpB MSM1463 Msp_0640 FdhA 4.1E−50 NONE formate dehydrogenase, 2.0E−39 alpha subunit related protein FlpC MSM1464 NONE MTH_1141 conserved protein (FlpE) 1.2E−18 MSM1465 Msp_0925 predicted arabinose efflux 1.3E−115 MTH_195 efflux pump antibiotic 9.5E−95 permease resistance protein MSM1466 NONE NONE MSM1467 NONE NONE MSM1468 Msp_0986 PurA 7.6E−136 MTH_615 adenylosuccinate 9.4E−143 synthetase MSM1469 Msp_1164 predicted ABC-type 2.4E−91 MTH_924 molybdate-binding 5.9E−06 nitrate/sulfonate/bicarbonate periplasmic protein transport system, periplasmic solute-binding protein MSM1470 NONE NONE MSM1471 Msp_0919 predicted acyl-CoA synthetase 2.3E−237 NONE succinyl-CoA synthetase, 2.5E−07 alpha subunit MSM1472 NONE MTH_752 conserved protein 3.7E−77 MSM1473 Msp_0575 predicted metal-dependent 2.9E−79 MTH_751 conserved protein 9.4E−72 hydrolase MSM1474 Msp_0579 AroC 7.2E−124 MTH_748 chorismate synthase 4.7E−125 MSM1475 Msp_0497 putative endonuclease III 1.0E−14 MTH_746 endonuclease III related 2.1E−51 protein MSM1476 Msp_0416 HemB 6.2E−102 MTH_744 porphobilinogen 3.6E−102 synthase MSM1477 Msp_0428 predicted ATP:dephospho-CoA 1.7E−58 MTH_743 conserved protein 5.9E−70 triphosphoribosyl transferase MSM1478 Msp_0429 PheS 2.6E−165 MTH_742 phenylalanyl-tRNA 5.5E−170 synthetase MSM1479 NONE MTH_212 exodeoxyribonuclease 2.4E−73 MSM1480 Msp_1260 predicted hydrolase 1.5E−59 MTH_209 conserved protein 1.1E−77 MSM1481 Msp_1281 conserved hypothetical protein 6.5E−59 MTH_208 DNA-dependent DNA 2.0E−69 polymerase family B (PolB2) MSM1482 NONE NONE MSM1483 Msp_0195 ABC-type multidrug transport 2.0E−41 MTH_1093 ABC transporter (ATP- 1.4E−54 system, ATP-binding protein binding MSM1484 Msp_0196 ABC-type multidrug transport 8.1E−29 MTH_1486 conserved protein 1.0E−19 system, permease protein MSM1485 Msp_0440 member of asn/thr-rich large protein 3.3E−06 NONE family MSM1486 Msp_1280 30S ribosomal protein S8e 6.6E−34 MTH_207 ribosomal protein S8 1.5E−41 MSM1487 NONE MTH_199 unknown 9.6E−31 MSM1488 Msp_0977 conserved hypothetical protein 3.1E−27 MTH_200 cobalamin biosynthesis 3.0E−50 protein M related protein MSM1489 Msp_0474 hypothetical protein 1.2E−09 MTH_1346 unknown 1.3E−177 MSM1490 Msp_0474 hypothetical protein 7.1E−06 MTH_201 unknown 4.9E−11 MSM1491 Msp_0474 hypothetical protein 9.8E−08 MTH_1346 unknown 1.3E−159 MSM1492 Msp_1279 HypE1 1.0E−122 MTH_205 hydrogenase 3.2E−126 expression/formation protein HypE MSM1493 Msp_1278 conserved hypothetical membrane- 1.3E−21 MTH_204 conserved protein 4.3E−19 spanning protein MSM1494 NONE NONE MSM1495 Msp_1089 predicted nuclease 1.8E−40 MTH_494 thermonuclease 8.5E−39 precursor MSM1496 Msp_0024 hypothetical protein 4.5E−67 NONE MSM1497 NONE MTH_1785 coenzyme PQQ 6.4E−57 synthesis protein MSM1498 Msp_1228 predicted helicase 2.1E−131 NONE ATP-dependent RNA 3.8E−114 helicase, elF-4A family MSM1499 Msp_1188 predicted transcriptional regulator 8.1E−61 MTH_163 conserved protein 2.5E−62 MSM1500 Msp_1189 RecJ 1.5E−114 MTH_164 single-stranded DNA 1.1E−116 exonuclease RecJ related protein MSM1501 Msp_1190 signal recognition particle, 19 kDa 4.0E−20 MTH_165 signal recognition particle 9.3E−17 protein 19 kDa protein MSM1502 Msp_0223 predicted UDP-galactopyranose 3.6E−65 MTH_344 UDP-galactopyranose 2.4E−80 mutase mutase MSM1503 Msp_0215 predicted glycosyltransferase 4.0E−39 MTH_884 teichoic acid biosynthesis 2.4E−06 related protein MSM1504 Msp_1191 HemD 2.2E−49 MTH_166 uroporphyrinogen III 1.1E−52 synthase MSM1505 NONE NONE MSM1506 NONE NONE MSM1507 Msp_0215 predicted glycosyltransferase 5.6E−34 MTH_884 teichoic acid biosynthesis 7.4E−10 related protein MSM1508 NONE NONE MSM1509 NONE NONE MSM1510 NONE NONE MSM1511 NONE NONE MSM1512 Msp_0060 putative lipooligosaccharide 7.0E−62 NONE cholinephosphotransferase MSM1513 Msp_0662 putative aspartate aminotransferase 2.7E−37 MTH_1601 aspartate 1.9E−41 aminotransferase MSM1514 Msp_1333 predicted dehydrogenase 1.3E−06 NONE 3-chlorobenzoate-3,4- 8.7E−09 dioxygenase dyhydrogenase related protein MSM1515 Msp_0060 putative lipooligosaccharide 1.1E−24 NONE cholinephosphotransferase MSM1516 Msp_1326 HisC 1.7E−26 MTH_1587 histidinol-phosphate 5.5E−22 aminotransferase MSM1517 NONE MTH_1495 omithine cyclodeaminase 1.2E−15 MSM1518 Msp_0017 conserved hypothetical protein 1.2E−11 NONE MSM1519 NONE NONE MSM1520 NONE NONE MSM1521 NONE NONE MSM1522 NONE NONE MSM1523 NONE NONE MSM1524 NONE NONE MSM1525 NONE NONE MSM1526 Msp_0772 hypothetical membrane-spanning 2.3E−15 MTH_252 conserved protein 7.1E−19 protein MSM1527 NONE NONE MSM1528 Msp_0608 predicted transcriptional regulator 1.9E−04 MTH_700 conserved protein 1.1E−04 MSM1529 NONE NONE MSM1530 NONE NONE MSM1531 Msp_0691 predicted Na+-dependent 1.3E−131 NONE transporter MSM1532 Msp_0691 predicted Na+-dependent 2.0E−137 NONE transporter MSM1533 Msp_1465 member of asn/thr-rich large protein 7.2E−12 MTH_1074 putative membrane 3.7E−06 family protein MSM1534 Msp_0590 member of asn/thr-rich large protein 2.0E−24 MTH-1074 putative membrane 3.0E−123 family protein MSM1535 Msp_1114 predicted dTDP-D-glucose 4,6- 1.3E−10 NONE dTDP-glucose 4,6- 1.2E−06 dehydratase dehydratase MSM1536 Msp_0290 predicted pyridoxal phosphate- 6.9E−71 MTH_1188 pleiotropic regulatory 6.6E−71 dependent enzyme protein DegT MSM1537 Msp_0310 predicted 4.2E−04 NONE GTP:adenosylcobinamide- phosphate guanylyltransferase MSM1538 Msp_1202 predicted acetyltransferase 1.9E−08 NONE N-terminal 3.5E−06 acetyltransferase complex, subunit ARD1 MSM1539 NONE NONE MSM1540 NONE MTH_368 glycerol-3-phosphate 6.5E−48 dehydrogenase (NAD) MSM1541 NONE NONE MSM1542 Msp_0310 predicted 4.6E−06 MTH_1152 conserved protein 1.4E−04 GTP:adenosylcobinamide- phosphate guanylyltransferase MSM1543 NONE NONE MSM1544 Msp_0060 putative lipooligosaccharide 3.9E−22 NONE cholinephosphotransferase MSM1545 Msp_0495 predicted glycosyltransferase 1.3E−31 MTH_136 dolichyl-phosphate 1.4E−08 mannose synthase MSM1546 NONE NONE MSM1547 Msp_1195 PurC 3.9E−77 MTH_170 phosphoribosylamino- 6.8E−69 imidazolesuccinocarboxamide synthase MSM1548 Msp_1194 predicted 1.2E−25 MTH_169 conserved protein 4.5E−24 phosphoribosylformylglycinamidine synthase MSM1549 Msp_1193 PurQ 2.4E−75 MTH_168 phosphoribosylformylglycinamidine 6.8E−85 synthase I MSM1550 Msp_1192 CobA 6.2E−86 MTH_167 S-adenosyl-L-methionine 7.1E−90 uroporphyrinogen methyltransferase MSM1551 Msp_1196 GlmS 1.5E−201 MTH_171 glutamine-fructose-6- 1.5E−208 phosphate transaminase MSM1552 NONE NONE MSM1553 NONE NONE MSM1554 Msp_0141 member of asn/thr-rich large protein 1.1E−09 NONE family MSM1555 Msp_0076 conserved hypothetical protein 3.5E−60 MTH_175 conserved protein 4.7E−77 MSM1556 Msp_1344 conserved hypothetical membrane- 6.5E−75 NONE spanning protein MSM1557 Msp_0520 predicted queuine/archaeosine 5.0E−219 MTH_176 tRNA-guanine 1.2E−206 tRNA-ribosyltransferase transglycosylase MSM1558 NONE MTH_1329 methyltransferase related 3.1E−04 protein MSM1559 Msp_0063 predicted polysaccharide 9.5E−74 MTH_379 O-antigen transporter 1.7E−72 biosynthesis protein related protein MSM1560 Msp_0448 predicted polysaccharide 1.3E−78 MTH-379 O-antigen transporter 4.9E−75 biosynthesis protein related protein MSM1561 Msp_0117 predicted 3-hydroxy-3- 3.6E−145 MTH_792 3-hydroxy-3- 3.4E−145 methylglutaryl CoA synthase methylglutaryl-CoA- synthase MSM1562 Msp_0116 predicted thiolase 2.1E−156 MTH_793 lipid-transfer protein 3.5E−168 (sterol or nonspecific) MSM1563 NONE NONE MSM1564 Msp_0087 CbiT 4.6E−05 NONE MSM1565 Msp_1226 CobQ 9.4E−154 MTH_787 cobyric acid synthase 1.1E−162 MSM1566 Msp_0233 conserved hypothetical protein 2.3E−22 NONE MSM1567 Msp_0762 member of asn/thr-rich large protein 7.2E−35 MTH_1485 serine/threonine protein 5.1E−13 family kinase related protein MSM1568 NONE NONE MSM1569 Msp_1227 predicted ATP-dependent protease 2.4E−226 MTH_785 ATP-dependent protease 9.0E−241 LA MSM1570 Msp_0557 hypothetical protein 1.1E−127 MTH_530 UDP-N-acetylmuramyl 2.6E−25 tripeptide synthetase related protein MSM1571 NONE NONE MSM1572 Msp_0683 hypothetical protein 4.9E−61 NONE MSM1573 NONE NONE MSM1574 Msp_0797 predicted nitroreductase 6.3E−10 MTH_120 NADPH-oxidoreductase 4.2E−11 MSM1575 Msp_1055 hypothetical membrane-spanning 7.8E−04 MTH_521 unknown 8.2E−05 protein MSM1576 NONE NONE MSM1577 Msp_1229 ribose-phosphate 1.2E−84 MTH_784 ribose-phosphate 1.0E−88 pyrophosphokinase pyrophosphokinase MSM1578 NONE NONE MSM1579 Msp_0573 UvrB 1.2E−247 MTH_442 excinuclease ABC 1.2E−261 subunit B MSM1580 NONE NONE MSM1581 Msp_0574 UvrA 0.0E+00 MTH_443 excinuclease ABC 0.0E+00 subunit A MSM1582 Msp_0603 conserved hypothetical membrane- 5.6E−85 MTH_465 unknown 4.8E−84 spanning protein MSM1583 Msp_1178 predicted helicase 7.4E−193 MTH_656 ATP-dependent RNA 2.1E−232 helicase related protein MSM1584 Msp_1119 conserved hypothetical protein 1.0E−37 MTH_641 conserved protein 2.9E−29 MSM1585 Msp_0983 member of asn/thr-rich large protein 5.5E−38 MTH_911 probable surface protein 9.9E−06 family MSM1586 Msp_0713 member of asn/thr-rich large protein 1.8E−52 MTH_911 probable surface protein 3.7E−14 family MSM1587 Msp_0590 member of asn/thr-rich large protein 6.0E−44 MTH_716 cell surface glycoprotein 1.2E−06 family (s-layer protein) MSM1588 NONE NONE MSM1589 NONE NONE MSM1590 Msp_0619 member of asn/thr-rich large protein 2.5E−48 MTH_716 cell surface glycoprotein 1.3E−07 family (s-layer protein) MSM1591 Msp_1118 conserved hypothetical protein 1.0E−37 MTH_639 conserved protein 5.6E−42 MSM1592 Msp_0205 predicted ABC-type 9.8E−72 MTH_1370 ABC transporter (ATP- 1.5E−20 polysaccharide/polyol phosphate binding protein) export system, ATP-binding protein MSM1593 Msp_0204 predicted ABC-type 1.3E−53 MTH_1092 putative membrane 5.7E−11 polysaccharide/polyol phosphate protein export system, permease protein MSM1594 Msp_0442 predicted glycosyltransferase 4.4E−60 MTH_884 teichoic acid biosynthesis 1.5E−07 related protein MSM1595 Msp_0929 predicted helicase 6.7E−04 NONE MSM1596 Msp_0017 conserved hypothetical protein 1.7E−28 NONE MSM1597 NONE NONE MSM1598 NONE NONE MSM1599 NONE NONE MSM1600 NONE NONE MSM1601 Msp_0692 hypothetical membrane-spanning 1.3E−07 NONE protein MSM1602 Msp_0220 predicted glycosyltransferase 6.9E−20 MTH_361 teichoic acid biosynthesis 1.7E−04 protein RodC related protein MSM1603 NONE MTH_637 conserved protein 1.1E−20 MSM1604 Msp_1101 predicted UDP-glucose 1.2E−103 MTH_634 UTP-glucose-1- 7.6E−109 pyrophosphorylase phosphate uridylyltransferase MSM1605 NONE NONE MSM1606 Msp_0612 predicted arylsulfatase regulatory 4.8E−102 MTH_114 arylsulfatase regulatory 1.9E−64 protein protein MSM1607 Msp_1060 hypothetical protein 2.4E−13 MTH_121 unknown 1.2E−05 MSM1608 Msp_1350 putative oxidoreductase 5.9E−97 MTH_907 conserved protein 8.1E−50 MSM1609 NONE MTH_924 molybdate-binding 6.6E−23 periplasmic protein MSM1610 Msp_0342 PstC 1.1E−15 MTH_921 anion transport system 6.4E−25 permease protein MSM1611 Msp_1000 predicted ABC-type 1.7E−28 MTH_920 anion permease 2.4E−34 nitrate/sulfonate/bicarbonate transport system, ATB-binding protein MSM1612 Msp_0210 predicted UDP-glucose 6- 6.3E−93 MTH_836 UDP-N-acetyl-D- 5.4E−24 dehydrogenase mannosaminuronic acid dehydrogenase MSM1613 NONE NONE MSM1614 Msp_0394 predicted transcriptional regulator 1.3E−74 MTH_126 inosine-5′- 2.1E−97 monophosphate dehydrogenase related protein VII MSM1615 Msp_0395 putative deoxyhypusine synthase 7.4E−106 MTH_127 deoxyhypusine synthase 4.6E−95 MSM1616 Msp_0396 hypothetical membrane-spanning 4.0E−27 MTH_128 unknown 6.2E−27 protein MSM1617 Msp_0397 PyrF 1.9E−66 MTH_129 orotidine 5′ 4.3E−67 monophosphate decarboxylase MSM1618 Msp_0398 CbiM1 6.0E−72 MTH_130 cobalamin biosynthesis 9.5E−79 protein M MSM1619 Msp_0399 CbiN 3.0E−31 MTH_131 cobalt transport protein N 7.2E−26 MSM1620 Msp_0400 CbiQ1 3.0E−38 MTH_132 cobalt transport protein Q 3.4E−42 MSM1621 Msp_0401 CbiO1 6.0E−88 MTH_133 cobalt transport ATP- 9.3E−88 binding protein O MSM1622 Msp_1239 RibC 6.9E−55 MTH_134 riboflavin synthase 2.3E−61 MSM1623 Msp_0541 predicted glycosyltransferase 2.1E−46 MTH_136 dolichyl-phosphate 6.1E−52 mannose synthase MSM1624 Msp_0542 hypothetical membrane-spanning 9.4E−19 MTH_137 unknown 1.2E−18 protein MSM1625 Msp_1044 TfrB 3.2E−34 MTH_1850 fumarate reductase 7.6E−33 MSM1626 Msp_1044 TfrB 3.0E−07 MTH_140 conserved protein 4.8E−107 MSM1627 Msp_0989 predicted glycosyltransferase 9.5E−11 MTH_377 dolichyl-phosphate 2.0E−11 mannose synthase related protein MSM1628 Msp_0430 conserved hypothetical protein 1.9E−75 MTH_141 conserved protein 7.0E−99 MSM1629 Msp_0431 GuaB 2.1E−163 MTH_142 inosine-5′- 1.5E−174 monophosphate dehydrogenase MSM1630 Msp_1253 50S ribosomal protein L37Ae 6.0E−33 MTH_681 ribosomal protein L37a 1.1E−36 MSM1631 NONE NONE MSM1632 Msp_1254 partially conserved hypothetical 1.0E−21 MTH_680 conserved protein 1.4E−15 protein MSM1633 Msp_1255 conserved hypothetical protein 1.0E−12 MTH_679 unknown 5.3E−14 MSM1634 Msp_1256 partially conserved hypothetical 2.5E−27 MTH_678 conserved protein 2.1E−35 protein MSM1635 NONE MTH_677 unknown 1.7E−10 MSM1636 Msp_1257 conserved hypothetical protein 2.6E−39 MTH_669 phosphoribosylformimino- 1.3E−58 5-aminoimidazole carboxamide ribotide isomeras related protein MSM1637 Msp_0173 hypothetical membrane-spanning 9.9E−08 NONE protein MSM1638 Msp_1259 hypothetical membrane-spanning 1.6E−09 MTH_667 unknown 3.0E−11 protein MSM1639 Msp_0519 predicted Co/Zn/Cd cation 4.1E−16 MTH_1893 cation efflux system 3.7E−17 transporter protein (zinc/cadmium) MSM1640 Msp_0482 hypothetical membrane-spanning 1.8E−38 NONE protein MSM1641 NONE NONE MSM1642 NONE NONE MSM1643 NONE NONE MSM1644 NONE NONE MSM1645 NONE NONE MSM1646 NONE NONE MSM1647 NONE NONE MSM1648 NONE NONE MSM1649 NONE NONE MSM1650 Msp_0260 hypothetical protein 7.9E−04 NONE MSM1651 NONE NONE MSM1652 NONE NONE MSM1653 NONE NONE MSM1654 NONE NONE MSM1655 Msp_1059 hypothetical protein 1.3E−05 NONE MSM1656 NONE NONE MSM1657 Msp_0793 hypothetical protein 4.9E−06 NONE MSM1658 NONE NONE MSM1659 NONE NONE MSM1660 NONE NONE MSM1661 NONE NONE MSM1662 NONE NONE MSM1663 NONE NONE MSM1664 NONE NONE MSM1665 NONE NONE MSM1666 Msp_0946 conserved hypothetical protein 1.2E−05 NONE MSM1667 NONE NONE MSM1668 NONE NONE MSM1669 NONE NONE MSM1670 Msp_0113 conserved hypothetical protein 1.8E−04 NONE MSM1671 NONE NONE MSM1672 NONE NONE MSM1673 Msp_0474 hypothetical protein 4.6E−04 NONE MSM1674 Msp_0822 hypothetical protein 2.5E−04 NONE MSM1675 NONE NONE MSM1676 NONE NONE MSM1677 NONE NONE MSM1678 NONE NONE MSM1679 NONE NONE MSM1680 NONE NONE MSM1681 NONE NONE MSM1682 NONE NONE MSM1683 NONE NONE MSM1684 Msp_0912 member of asn/thr-rich large protein 2.1E−06 MTH_412 conserved protein 4.7E−04 family MSM1685 NONE NONE MSM1686 NONE NONE MSM1687 Msp_0658 hypothetical membrane-spanning 8.1E−07 MTH_1459 unknown 3.6E−07 protein MSM1688 NONE NONE MSM1689 NONE NONE MSM1690 NONE NONE MSM1691 Msp_1039 partially conserved hypothetical 1.5E−07 MTH_357 conserved protein 5.3E−08 membrane-spanning protein MSM1692 NONE NONE MSM1693 Msp_1258 predicted ribokinase 6.9E−39 MTH_668 unknown 1.8E−20 MSM1694 Msp_0929 predicted helicase 3.6E−193 MTH_487 DNA helicase related 4.9E−304 protein MSM1695 Msp_0572 UvrC 6.3E−164 MTH_441 excinuclease ABC 5.6E−161 subunit C MSM1696 Msp_1548 hypothetical protein 1.7E−08 NONE MSM1697 NONE NONE MSM1698 Msp_0439 methyl-coenzyme M reductase, 2.7E−147 NONE methyl coenzyme M 5.4E−179 component A2-like protein reductase system, component A2 homolog MSM1699 Msp_0438 predicted universal stress protein 2.1E−14 MTH_153 conserved protein 5.4E−21 MSM1700 Msp_1061 hypothetical protein 7.3E−12 MTH_278 ferredoxin 1.4E−20 MSM1701 Msp_1062 predicted dehydrogenase 4.0E−130 MTH_277 bacteriochlorophyll 8.8E−147 synthase 43 kDa subunit MSM1702 Msp_1088 ExoB 7.9E−102 MTH_631 UDP-glucose 4- 3.5E−97 epimerase MSM1703 NONE MTH_647 unknown 5.0E−25 MSM1704 Msp_1122 PurF 1.4E−143 MTH_646 amidophosphoribosyltransferase 1.2E−156 MSM1705 Msp_1121 predicted peptidase 2.4E−100 MTH_645 collagenase 3.7E−100 MSM1706 Msp_1513 hypothetical membrane-spanning 2.9E−24 NONE protein MSM1707 Msp_1120 NifH 2.6E−96 MTH_643 nitrogenase NifH subunit 5.5E−99 MSM1708 NONE NONE MSM1709 Msp_0440 member of asn/thr-rich large protein 1.3E−35 MTH_716 cell surface glycoprotein 2.4E−04 family (s-layer protein) MSM1710 Msp_1277 SerS 1.9E−187 MTH_1455 threonyl-tRNA 5.3E−06 synthetase MSM1711 Msp_0725 hypothetical protein 1.0E−08 NONE MSM1712 Msp_0852 predicted ferritin 8.4E−50 MTH_158 ferritin like protein (RsgA) 2.3E−59 MSM1713 Msp_1008 predicted regulatory protein 5.4E−32 MTH_162 unknown 1.5E−41 MSM1714 Msp_1040 coenzyme F390 synthetase II 6.3E−164 MTH_161 coenzyme F390 3.7E−164 synthetase III MSM1715 Msp_1110 CobN 1.7E−68 MTH_714 magnesium chelatase 0.0E+00 subunit MSM1716 Msp_0590 member of asn/thr-rich large protein 2.5E−16 MTH_717 unknown 3.9E−25 family MSM1717 Msp_1105 predicted transporter 1.9E−52 MTH_672 unknown 2.3E−52 MSM1718 Msp_1106 conserved hypothetical membrane- 2.0E−50 MTH_671 unknown 3.7E−61 spanning protein MSM1719 Msp_1107 conserved hypothetical membrane- 4.1E−25 MTH_670 unknown 1.2E−32 spanning protein MSM1720 Msp_1533 RpoM1 7.3E−28 MTH_1314 transcription elongation 8.6E−30 factor TFIIS MSM1721 NONE NONE MSM1722 Msp_0965 predicted nitroreductase 6.9E−16 MTH_120 NADPH-oxidoreductase 7.3E−33 MSM1723 Msp_1238 N(5),N(10)- 6.7E−105 NONE N5,N10-methenyl- 2.1E−138 methenyltetrahydromethanopterin tetrahydromethanopterin cyclohydrolase cyclohydrolase MSM1724 Msp_0961 hypothetical membrane-spanning 3.1E−36 MTH_1192 conserved protein 9.2E−25 protein MSM1725 Msp_0961 hypothetical membrane-spanning 5.7E−28 MTH_1192 conserved protein 1.6E−30 protein MSM1726 Msp_0879 hypothetical membrane-spanning 9.0E−30 MTH_1192 conserved protein 1.3E−25 protein MSM1727 Msp_0844 predicted multimeric flavodoxin 1.2E−18 MTH_135 conserved protein 1.9E−18 MSM1728 NONE NONE MSM1729 Msp_0587 hypothetical membrane-spanning 5.0E−29 MTH_520 unknown 3.9E−10 protein MSM1730 Msp_0607 hypothetical membrane-spanning 6.5E−20 MTH_1192 conserved protein 1.2E−26 protein MSM1731 Msp_0714 predicted short chain 1.7E−115 NONE dehydrogenase MSM1732 Msp_1548 hypothetical protein 8.2E−07 NONE MSM1733 Msp_0789 rubrerythrin 1.6E−39 MTH_756 rubrerythrin 3.3E−43 MSM1734 Msp_1237 ThyA 8.9E−28 MTH_774 thymidylate synthase 7.2E−26 MSM1735 Msp_0777 member of asn/thr-rich large protein 7.4E−116 MTH_716 cell surface glycoprotein 1.4E−06 family (s-layer protein) MSM1736 NONE NONE MSM1737 NONE NONE MSM1738 Msp_0154 member of asn/thr-rich large protein 2.3E−06 NONE family MSM1739 Msp_0987 hypothetical membrane-spanning 2.7E−07 MTH_521 unknown 1.4E−05 protein MSM1740 Msp_1323 conserved hypothetical protein 1.1E−16 MTH_83 O-linked GlcNAc 4.7E−38 transferase MSM1741 Msp_0113 conserved hypothetical protein 5.0E−05 NONE MSM1742 Msp_0482 hypothetical membrane-spanning 2.7E−76 NONE protein MSM1743 Msp_0113 conserved hypothetical protein 4.1E−06 NONE MSM1744 NONE NONE MSM1745 Msp_0344 predicted phosphate uptake 2.0E−04 NONE regulator MSM1746 NONE NONE MSM1747 Msp_0911 member of asn/thr-rich large protein 8.1E−06 NONE family MSM1748 NONE NONE MSM1749 NONE NONE MSM1750 NONE NONE MSM1751 Msp_0113 conserved hypothetical protein 6.3E−15 NONE MSM1752 Msp_0702 conserved hypothetical protein 1.2E−59 MTH_1210 mrr restriction system 3.4E−42 related protein MSM1753 Msp_0465 conserved hypothetical membrane- 6.7E−04 NONE spanning protein MSM1754 Msp_1328 putative ATP-dependent protease 3.6E−06 NONE La MSM1755 Msp_0219 conserved hypothetical protein 6.7E−04 NONE MSM1756 Msp_0976 hypothetical protein 2.8E−05 NONE MSM1757 NONE NONE MSM1758 NONE NONE MSM1759 NONE NONE MSM1760 NONE NONE MSM1761 Msp_0113 conserved hypothetical protein 7.6E−07 MTH_540 intracellular protein 2.7E−05 transport protein MSM1762 NONE NONE MSM1763 Msp_1533 RpoM1 4.6E−10 MTH_1314 transcription elongation 3.1E−09 factor TFIIS MSM1764 Msp_0226 hypothetical protein 8.9E−04 NONE MSM1765 NONE NONE MSM1766 Msp_1323 conserved hypothetical protein 4.8E−15 MTH_83 O-linked GlcNAc 3.4E−35 transferase MSM1767 Msp_1548 hypothetical protein 1.3E−04 NONE MSM1768 NONE NONE MSM1769 Msp_0724 hypothetical membrane-spanning 2.1E−08 MTH_1277 unknown 8.9E−05 protein MSM1770 Msp_0934 conserved hypothetical membrane- 1.4E−17 MTH_518 conserved protein 3.4E−19 spanning protein MSM1771 Msp_0128 predicted helicase 5.0E−19 MTH_511 DNA helicase II 1.1E−26 MSM1772 Msp_0725 hypothetical protein 4.0E−11 MTH_470 conserved protein 1.2E−04 MSM1773 Msp_1548 hypothetical protein 4.3E−07 MTH_521 unknown 7.7E−05 MSM1774 NONE NONE MSM1775 NONE NONE MSM1776 NONE NONE MSM1777 Msp_0799 predicted transcriptional regulator 3.3E−05 MTH_671 unknown 2.6E−04 MSM1778 Msp_0726 hypothetical protein 2.7E−69 NONE MSM1779 Msp_0725 hypothetical protein 2.6E−119 NONE MSM1780 Msp_1055 hypothetical membrane-spanning 1.1E−10 MTH_1277 unknown 2.7E−06 protein MSM1781 Msp_0725 hypothetical protein 2.4E−13 MTH_470 conserved protein 1.4E−05 MSM1782 NONE NONE MSM1783 NONE NONE MSM1784 NONE NONE MSM1785 NONE NONE MSM1786 Msp_1323 conserved hypothetical protein 4.1E−07 MTH_83 O-linked GlcNAc 6.9E−12 transferase MSM1787 Msp_1323 conserved hypothetical protein 5.6E−09 MTH_72 O-linked GlcNAc 3.6E−16 transferase MSM1788 Msp_1323 conserved hypothetical protein 7.3E−11 MTH_83 O-linked GlcNAc 2.0E−20 transferase MSM1789 Msp_0757 predicted ATPase 2.5E−08 NONE MSM1790 Msp_0757 predicted ATPase 4.9E−08 NONE MSM1791 NONE MTH_512 unknown 1.1E−25 MSM1792 Msp_0764 predicted nicotinate 1.7E−193 NONE phosphoribosyltransferase MSM1793 NONE NONE MSM1794 Msp_1103 member of asn/thr-rich large protein 1.5E−04 MTH_512 unknown 1.2E−24 family MSM1795 Msp_0757 predicted ATPase 1.7E−99 NONE

TABLE 9 Cluster of Orthologous Groups (COG) represented in the M. smithii PS proteome A. Summary Number of M. smithii genes in COG Code Functional Category 136 J Translation 60 K Transcription 78 L Replication, Recombination and Repair 3 B Chromatin Structure and Dynamics 6 D Cell Cycle Control 26 V Defense Mechanisms 8 T Signal Transduction Mechanisms 59 M Cell Wall/Membrane Biogenesis 3 N Cell Motility 1 Z Cytoskeleton 17 U Intracellular Trafficking and Secretion 41 O Post-translational Modification, Protein Turnover, Chaperones 121 C Energy Production and Conversion 30 G Carbohydrate Transport and Metabolism 82 E Amino Acid Transport and Metabolism 42 F Nucleic Acid Transport and Metabolism 92 H Coenzyme Transport and Metabolism 18 I Lipid Transport and Metabolism 57 P Inorganic Ion Transport and Metabolism 1 Q Secondary Metabolites Biosynthesis, Transport and Catabolism 201 R General Function Prediction Only 171 S Function Unknown 491 — Not in COGs B. M. smithii genes in each COG # in COG COG Description M. smithii gene(s) Translation (J) 1 COG0008 Glutamyl- and glutaminyl-tRNA synthetases MSM1452 1 COG0009 Putative translation factor (SUA5) MSM0612 1 COG0012 Predicted GTPase, probable translation factor MSM1164 1 COG0013 Alanyl-tRNA synthetase MSM0619 1 COG0016 Phenylalanyl-tRNA synthetase alpha subunit MSM1478 1 COG0017 Aspartyl/asparaginyl-tRNA synthetases MSM1236 1 COG0018 Arginyl-tRNA synthetase MSM1231 1 COG0023 Translation initiation factor 1 (elF-1/SUI1) and related MSM0754 proteins 1 COG0024 Methionine aminopeptidase MSM1120 1 COG0030 Dimethyladenosine transferase (rRNA methylation) MSM1374 1 COG0042 tRNA-dihydrouridine synthase MSM0972 1 COG0048 Ribosomal protein S12 MSM0901 1 COG0049 Ribosomal protein S7 MSM0900 1 COG0051 Ribosomal protein S10 MSM0897 1 COG0060 Isoleucyl-tRNA synthetase MSM1341 1 COG0064 Asp-tRNAAsn/Glu-tRNAGln amidotransferase B MSM1101 subunit (PET112 homolog) 1 COG0072 Phenylalanyl-tRNA synthetase beta subunit MSM0277 1 COG0080 Ribosomal protein L11 MSM0623 1 COG0081 Ribosomal protein L1 MSM0622 1 COG0087 Ribosomal protein L3 MSM0762 1 COG0088 Ribosomal protein L4 MSM0761 1 COG0089 Ribosomal protein L23 MSM0760 1 COG0090 Ribosomal protein L2 MSM0759 1 COG0091 Ribosomal protein L22 MSM0757 1 COG0092 Ribosomal protein S3 MSM0756 1 COG0093 Ribosomal protein L14 MSM0751 1 COG0094 Ribosomal protein L5 MSM0748 1 COG0096 Ribosomal protein S8 MSM0746 1 COG0097 Ribosomal protein L6P/L9E MSM0745 1 COG0098 Ribosomal protein S5 MSM0741 1 COG0099 Ribosomal protein S13 MSM1425 1 COG0100 Ribosomal protein S11 MSM1427 1 COG0101 Pseudouridylate synthase MSM0855 1 COG0102 Ribosomal protein L13 MSM1430 1 COG0103 Ribosomal protein S9 MSM1431 1 COG0124 Histidyl-tRNA synthetase MSM1181 1 COG0130 Pseudouridine synthase MSM0732 1 COG0143 Methionyl-tRNA synthetase MSM0071 1 COG0154 Asp-tRNAAsn/Glu-tRNAGln amidotransferase A MSM1253 subunit and related amidases 1 COG0162 Tyrosyl-tRNA synthetase MSM0513 1 COG0172 Seryl-tRNA synthetase MSM1710 1 COG0180 Tryptophanyl-tRNA synthetase MSM0216 1 COG0182 Predicted translation initiation factor 2B subunit, elF- MSM0804 2B alpha/beta/delta family 1 COG0184 Ribosomal protein S15P/S13E MSM1194 1 COG0185 Ribosomal protein S19 MSM0758 1 COG0186 Ribosomal protein S17 MSM0752 1 COG0197 Ribosomal protein L16/L10E MSM0989 1 COG0198 Ribosomal protein L24 MSM0750 1 COG0199 Ribosomal protein S14 MSM0747 1 COG0200 Ribosomal protein L15 MSM0739 1 COG0215 Cysteinyl-tRNA synthetase MSM0268 1 COG0231 Translation elongation factor P (EF-P)/translation MSM0877 initiation factor 5A (elF-5A) 1 COG0244 Ribosomal protein L10 MSM0621 1 COG0255 Ribosomal protein L29 MSM0755 1 COG0256 Ribosomal protein L18 MSM0742 1 COG0293 23S rRNA methylase MSM0508 1 COG0343 Queuine/archaeosine tRNA-ribosyltransferase MSM1557 1 COG0423 Glycyl-tRNA synthetase (class II) MSM0403 1 COG0441 Threonyl-tRNA synthetase MSM1214 1 COG0442 Prolyl-tRNA synthetase MSM0287 1 COG0480 Translation elongation factors (GTPases) MSM0899 1 COG0495 Leucyl-tRNA synthetase MSM1172 1 COG0522 Ribosomal protein S4 and related proteins MSM1426 1 COG0525 Valyl-tRNA synthetase MSM0275 1 COG0532 Translation initiation factor 2 (IF-2; GTPase) MSM0202 1 COG0565 rRNA methylase MSM0394 1 COG0621 2-methylthioadenine synthetase MSM0845 1 COG0689 RNase PH MSM0242 1 COG1093 Translation initiation factor 2, alpha subunit (elF- MSM1133 2alpha) 1 COG1096 Predicted RNA-binding protein (consists of S1 MSM1357 domain and a Zn-ribbon domain) 1 COG1097 RNA-binding protein Rrp4 and related proteins MSM0243 (contain S1 domain and KH domain) 1 COG1258 Predicted pseudouridylate synthase MSM1361 1 COG1325 Predicted exosome subunit MSM0297 1 COG1358 Ribosomal protein HS6-type (S12/L30/L7a) MSM0206 1 COG1369 RNase P/RNase MRP subunit POP5 MSM0246 1 COG1383 Ribosomal protein S17E MSM0833 1 COG1384 Lysyl-tRNA synthetase (class I) MSM1387 1 COG1471 Ribosomal protein S4E MSM0749 1 COG1491 Predicted RNA-binding protein MSM1375 1 COG1498 Protein implicated in ribosomal biogenesis, Nop56p MSM1046 homolog 1 COG1500 Predicted exosome subunit MSM0244 1 COG1503 Peptide chain release factor 1 (eRF1) MSM0891 1 COG1514 2′-5′ RNA ligase MSM0054 1 COG1534 Predicted RNA-binding protein containing KH MSM0710 domain, possibly ribosomal protein 2 COG1549 Queuine tRNA-ribosyltransferases, contain PUA MSM0633, MSM0797 domain 1 COG1552 Ribosomal protein L40E MSM0125 1 COG1588 RNase P/RNase MRP subunit p29 MSM0753 1 COG1601 Translation initiation factor 2, beta subunit (elF- MSM0511 2beta)/elF-5 N-terminal domain 1 COG1603 RNase P/RNase MRP subunit p30 MSM0247 1 COG1631 Ribosomal protein L44E MSM1135 1 COG1632 Ribosomal protein L15E MSM0298 1 COG1670 Acetyltransferases, including N-acetylases of MSM1573 ribosomal proteins 1 COG1676 tRNA splicing endonuclease MSM0217 1 COG1717 Ribosomal protein L32E MSM0744 1 COG1727 Ribosomal protein L18E MSM1429 1 COG1736 Diphthamide synthase subunit DPH2 MSM1358 1 COG1746 tRNA nucleotidyltransferase (CCA-adding enzyme) MSM0053 1 COG1798 Diphthamide biosynthesis methyltransferase MSM0801 1 COG1841 Ribosomal protein L30/L7E MSM0740 1 COG1867 N2,N2-dimethylguanosine tRNA methyltransferase MSM1031 1 COG1889 Fibrillarin-like rRNA methylase MSM1047 1 COG1890 Ribosomal protein S3AE MSM0661 1 COG1911 Ribosomal protein L30E MSM0907 1 COG1976 Translation initiation factor 6 (elF-6) MSM0704 1 COG1997 Ribosomal protein L37AE/L43A MSM1630 1 COG1998 Ribosomal protein S27AE MSM0193 1 COG2004 Ribosomal protein S24E MSM0194 1 COG2007 Ribosomal protein S8E MSM1486 1 COG2016 Predicted RNA-binding protein (contains PUA MSM0183 domain) 1 COG2023 RNase P subunit RPR2 MSM0711 1 COG2051 Ribosomal protein S27E MSM1134 1 COG2053 Ribosomal protein S28E/S33 MSM0205 1 COG2075 Ribosomal protein L24E MSM0204 1 COG2092 Translation elongation factor EF-1beta MSM0602 1 COG2097 Ribosomal protein L31E MSM0705 1 COG2117 Predicted subunit of tRNA(5-methylaminomethyl-2- MSM0707 thiouridylate) methyltransferase, contains the PP-loop ATPase domain 1 COG2123 RNase PH-related exoribonuclease MSM0241 1 COG2125 Ribosomal protein S6E (S10) MSM0201 1 COG2126 Ribosomal protein L37E MSM0181 1 COG2139 Ribosomal protein L21E MSM1377 1 COG2147 Ribosomal protein L19E MSM0743 1 COG2157 Ribosomal protein L20A (L18A) MSM0703 1 COG2163 Ribosomal protein L14E/L6E/L27E MSM0733 1 COG2167 Ribosomal protein L39E MSM0706 1 COG2174 Ribosomal protein L34E MSM0735 1 COG2238 Ribosomal protein S19E (S16A) MSM0709 1 COG2260 Predicted Zn-ribbon RNA-binding protein MSM1132 1 COG2263 Predicted RNA methylase MSM0764 1 COG2511 Archaeal Glu-tRNAGln amidotransferase subunit E MSM0335 (contains GAD domain) 1 COG2519 tRNA(1-methyladenosine) methyltransferase and MSM1173 related methyltransferases 1 COG2888 Predicted Zn-ribbon RNA-binding protein with a MSM0603 function in translation 1 COG2890 Methylase of polypeptide chain release factors MSM1373 1 COG3277 RNA-binding protein involved in rRNA processing MSM0425 1 COG5256 Translation elongation factor EF-1alpha (GTPase) MSM0898 1 COG5257 Translation initiation factor 2, gamma subunit (elF- MSM0200 2gamma; GTPase) Transcription (K) 2 COG0085 DNA-directed RNA polymerase, beta subunit/140 kD MSM0910, MSM0911 subunit 2 COG0086 DNA-directed RNA polymerase, beta′ subunit/160 kD MSM0908, MSM0909 subunit 1 COG0195 Transcription elongation factor MSM0906 1 COG0202 DNA-directed RNA polymerase, alpha subunit/40 kD MSM1428 subunit 1 COG0250 Transcription antiterminator MSM0624 1 COG0571 dsRNA-specific ribonuclease MSM0176 1 COG0583 Transcriptional regulator MSM1390 3 COG0640 Predicted transcriptional regulators MSM0819, MSM1126, MSM1350 1 COG0789 Predicted transcriptional regulators MSM0949 1 COG0846 NAD-dependent protein deacetylases, SIR2 family MSM1087 1 COG0864 Predicted transcriptional regulators containing the MSM0364 CopG/Arc/MetJ DNA-binding domain and a metal- binding domain 1 COG1095 DNA-directed RNA polymerase, subunit E′ MSM0197 1 COG1293 Predicted RNA-binding protein homologous to MSM0778 eukaryotic snRNP 1 COG1308 Transcription factor homologous to NACalpha-BTF3 MSM0384 2 COG1309 Transcriptional regulator MSM0094, MSM0650 1 COG1321 Mn-dependent transcriptional regulator MSM0218 1 COG1378 Predicted transcriptional regulators MSM1445 1 COG1395 Predicted transcriptional regulator MSM0453 3 COG1396 Predicted transcriptional regulators MSM0026, MSM0329, MSM1528 1 COG1405 Transcription initiation factor TFIIIB, Brf1 MSM0424 subunit/Transcription initiation factor TFIIB 1 COG1476 Predicted transcriptional regulators MSM1150 1 COG1497 Predicted transcriptional regulator MSM1499 1 COG1522 Transcriptional regulators MSM1032 1 COG1581 Archaeal DNA-binding protein MSM1245 3 COG1594 DNA-directed RNA polymerase, subunit MSM1354, MSM1720, M/Transcription elongation factor TFIIS MSM1763 1 COG1644 DNA-directed RNA polymerase, subunit N MSM1432 (RpoN/RPB10) 1 COG1675 Transcription initiation factor IIE, alpha subunit MSM0631 1 COG1695 Predicted transcriptional regulators MSM1250 1 COG1733 Predicted transcriptional regulators MSM0864 1 COG1758 DNA-directed RNA polymerase, subunit K/omega MSM1433 1 COG1761 DNA-directed RNA polymerase, subunit L MSM1356 1 COG1777 Predicted transcriptional regulators MSM1107 1 COG1813 Predicted transcription factor, homolog of eukaryotic MSM0355 MBF1 3 COG1846 Transcriptional regulators MSM0413, MSM0600, MSM1230 2 COG1958 Small nuclear ribonucleoprotein (snRNP) homolog MSM0182, MSM1220 1 COG1996 DNA-directed RNA polymerase, subunit RPC10 MSM1631 (contains C4-type Zn-finger) 1 COG2012 DNA-directed RNA polymerase, subunit H, MSM0912 RpoH/RPB5 1 COG2093 DNA-directed RNA polymerase, subunit E″ MSM0196 1 COG2101 TATA-box binding protein (TBP), component of TFIID MSM0720 and TFIIIB 1 COG2183 Transcriptional accessory protein MSM1292 1 COG2207 AraC-type DNA-binding domain-containing proteins MSM0775 1 COG2524 Predicted transcriptional regulator, contains C- MSM1614 terminal CBS domains 2 COG2865 Predicted transcriptional regulator containing an HTH MSM0540, MSM1315 domain and an uncharacterized domain shared with the mammalian protein Schlafen 1 COG4008 Predicted metal-binding transcription factor MSM0969 3 COG4742 Predicted transcriptional regulator MSM0404, MSM0817, MSM0818 Replication, Recombination and Repair (L) 2 COG0084 Mg-dependent DNase MSM0097, MSM0416 1 COG0122 3-methyladenine DNA glycosylase/8-oxoguanine MSM1365 DNA glycosylase 1 COG0164 Ribonuclease HII MSM0979 2 COG0177 Predicted EndoIII-related endonuclease MSM0272, MSM1584 1 COG0178 Excinuclease ATPase subunit MSM1581 2 COG0188 Type IIA topoisomerase (DNA gyrase/topo II, MSM1353, MSM1775 topoisomerase IV), A subunit 5 COG0210 Superfamily I DNA and RNA helicases MSM0058, MSM0113, MSM0731, MSM1420, MSM1771 1 COG0258 5′-3′ exonuclease (including N-terminal domain of MSM0725 Poll) 1 COG0270 Site-specific DNA methylase MSM0531 1 COG0322 Nuclease subunit of the excinuclease complex MSM1695 1 COG0350 Methylated DNA-protein cysteine methyltransferase MSM1185 1 COG0358 DNA primase (bacterial type) MSM0427 2 COG0417 DNA polymerase elongation subunit (family B) MSM1041, MSM1481 3 COG0419 ATPase involved in DNA repair MSM0120, MSM0693, MSM1761 1 COG0420 DNA repair exonuclease MSM0121 2 COG0468 RecA/RadA recombinase MSM0611, MSM1333 2 COG0470 ATPase involved in DNA replication MSM1176, MSM1177 1 COG0550 Topoisomerase IA MSM0717 1 COG0556 Helicase subunit of the DNA excision repair complex MSM1579 3 COG0582 Integrase MSM0428, MSM1640, MSM1742 1 COG0592 DNA polymerase sliding clamp subunit (PCNA MSM1137 homolog) 2 COG0608 Single-stranded DNA-specific exonuclease MSM1193, MSM1500 1 COG0648 Endonuclease IV MSM0963 1 COG0708 Exonuclease III MSM1479 1 COG1041 Predicted DNA modification methylase MSM0352 1 COG1107 Archaea-specific RecJ-like exonuclease, contains MSM0260 DnaJ-type Zn finger domain 1 COG1111 ERCC4-like helicases MSM1187 2 COG1112 Superfamily I DNA and RNA helicases and helicase MSM1081, MSM1694 subunits 1 COG1193 Mismatch repair ATPase (MutS family) MSM0524 1 COG1241 Predicted ATPase involved in replication control, MSM0510 Cdc46/Mcm family 1 COG1311 Archaeal DNA polymerase II, small subunit/DNA MSM1271 polymerase delta, subunit B 1 COG1343 Uncharacterized protein predicted to be involved in MSM0163 DNA repair 1 COG1389 DNA topoisomerase VI, subunit B MSM0955 2 COG1468 RecB family exonuclease MSM0165, MSM1059 2 COG1518 Uncharacterized protein predicted to be involved in MSM0023, MSM0164 DNA repair 1 COG1525 Micrococcal nuclease (thermonuclease) homologs MSM1495 1 COG1533 DNA repair photolyase MSM0543 1 COG1570 Exonuclease VII, large subunit MSM0001 1 COG1583 Uncharacterized protein predicted to be involved in MSM0170 DNA repair (RAMP superfamily) 1 COG1591 Holliday junction resolvase - archaeal type MSM1098 1 COG1599 Single-stranded DNA-binding replication protein A MSM1332 (RPA), large (70 kD) subunit and related ssDNA- binding proteins 1 COG1637 Predicted nuclease of the RecB family MSM0497 1 COG1688 Uncharacterized protein predicted to be involved in MSM0167 DNA repair (RAMP superfamily) 1 COG1697 DNA topoisomerase VI, subunit A MSM0956 1 COG1793 ATP-dependent DNA ligase MSM0645 1 COG1857 Uncharacterized protein predicted to be involved in MSM0168 DNA repair 1 COG1933 Archaeal DNA polymerase II, large subunit MSM1384 1 COG2219 Eukaryotic-type DNA primase, large subunit MSM0073 1 COG2231 Uncharacterized protein related to Endonuclease III MSM1475 2 COG3335 Transposase and inactivated derivatives MSM0460, MSM1589 1 COG3359 Predicted exonuclease MSM0138 2 COG3415 Transposase and inactivated derivatives MSM0458, MSM1588 5 COG3464 Transposase and inactivated derivatives MSM0087, MSM0230, MSM0396, MSM1093, MSM1566 1 COG3666 Transposase and inactivated derivatives MSM1523 Chromatin Structure and Dynamics (B) 3 COG2036 Histones H3 and H4 MSM0213, MSM0844, MSM1260 Cell Cycle Control (D) 3 COG0037 Predicted ATPase of the PP-loop superfamily MSM0553, MSM1028, implicated in cell cycle control MSM1178 1 COG0489 ATPases involved in chromosome partitioning MSM0045 1 COG1077 Actin-like ATPase involved in cell morphogenesis MSM0980 1 COG1192 ATPases involved in chromosome partitioning MSM1241 Defense Mechanisms (V) 5 COG0534 Na+-driven multidrug efflux pump MSM0152, MSM0252, MSM0414, MSM1228, MSM1229 2 COG0577 ABC-type antimicrobial peptide transport system, MSM0856, MSM1400 permease component 2 COG0732 Restriction endonuclease S subunits MSM0157, MSM0158 2 COG0842 ABC-type multidrug transport system, permease MSM1248, MSM1484 component 6 COG1002 Type II restriction enzyme, methylase subunits MSM1743, MSM1744, MSM1745, MSM1746, MSM1747, MSM1748 3 COG1131 ABC-type multidrug transport system, ATPase MSM0593, MSM1249, component MSM1483 2 COG1132 ABC-type multidrug transport system, ATPase and MSM0773, MSM0774 permease components 1 COG1136 ABC-type antimicrobial peptide transport system, MSM0857 ATPase component 1 COG1715 Restriction endonuclease MSM1752 1 COG1968 Uncharacterized bacitracin resistance protein MSM1201 1 COG4845 Chloramphenicol O-acetyltransferase MSM0047 Signal Transduction Mechanisms (T) 3 COG0589 Universal stress protein UspA and related nucleotide- MSM0485, MSM0887, binding proteins MSM1699 5 COG3448 CBS-domain-containing membrane protein MSM0305, MSM0484, MSM0790, MSM1053, MSM1054 Cell Wall/Membrane Biogenesis (M) 1 COG0381 UDP-N-acetylglucosamine 2-epimerase MSM0853 3 COG0399 Predicted pyridoxal phosphate-dependent enzyme MSM0347, MSM1030, apparently involved in regulation of cell wall MSM1536 biogenesis 4 COG0438 Glycosyltransferase MSM0836, MSM1313, MSM1317, MSM1322 1 COG0449 Glucosamine 6-phosphate synthetase, contains MSM1551 amidotransferase and phosphosugar isomerase domains 14  COG0463 Glycosyltransferases involved in cell wall biogenesis MSM0423, MSM1290, MSM1294, MSM1297, MSM1310, MSM1311, MSM1312, MSM1316, MSM1323, MSM1324, MSM1328, MSM1545, MSM1623, MSM1627 2 COG0472 UDP-N-acetylmuramyl pentapeptide MSM0066, MSM0360 phosphotransferase/UDP-Nacetylglucosamine-1- phosphate transferase 1 COG0562 UDP-galactopyranose mutase MSM1502 1 COG0668 Small-conductance mechanosensitive channel MSM0493 1 COG0677 UDP-N-acetyl-D-mannosaminuronate dehydrogenase MSM1303 1 COG0707 pfam match to MurG; not predicted to be a MSM0638 carbohydrate active enzyme by CAZy 1 COG0750 Predicted membrane-associated Zn-dependent MSM1344 proteases 1 3 COG0769 UDP-N-acetylmuramyl tripeptide synthase MSM0359, MSM1139, MSM1570 1 COG0770 UDP-N-acetylmuramyl pentapeptide synthase MSM0880 1 COG0771 UDP-N-acetylmuramoylalanine-D-glutamate ligase MSM0118 1 COG0773 UDP-N-acetylmuramate-alanine ligase MSM1190 1 COG0794 Predicted sugar phosphate isomerase involved in MSM1391 capsule formation 1 COG1004 Predicted UDP-glucose 6-dehydrogenase MSM1612 1 COG1083 CMP-N-acetylneuraminic acid synthetase MSM0944 1 COG1087 UDP-glucose 4-epimerase MSM1702 1 COG1088 dTDP-D-glucose 4,6-dehydratase MSM1309 1 COG1091 dTDP-4-dehydrorhamnose reductase MSM1304 1 COG1209 dTDP-glucose pyrophosphorylase MSM1307 1 COG1210 UDP-glucose pyrophosphorylase MSM1604 1 COG1861 Spore coat polysaccharide biosynthesis protein F, MSM1537 CMP-KDO synthetase homolog 1 COG1887 Putative glycosyl/glycerophosphate transferases MSM1327 involved in teichoic acid biosynthesis TagF/TagB/EpsJ/RodC 1 COG1898 dTDP-4-dehydrorhamnose 3,5-epimerase and related MSM1308 enzymes 1 COG2089 Sialic acid synthase MSM1539 1 COG2148 Sugar transferases involved in lipopolysaccharide MSM1331 synthesis 1 COG2222 Predicted phosphosugar isomerases MSM0872 2 COG2230 Cyclopropane fatty acid synthase and related MSM0274, MSM0490 methyltransferases 1 COG2843 Putative enzyme of poly-gamma-glutamate MSM0700 biosynthesis (capsule formation) 1 COG3049 Penicillin V acylase and related amidases MSM0986 3 COG3475 LPS biosynthesis protein MSM1512, MSM1515, MSM1544 1 COG3764 Sortase (surface protein transpeptidase) MSM0984 1 COG3980 Spore coat polysaccharide biosynthesis protein, MSM1538 predicted glycosyltransferase Cell Motility (N) 1 COG3351 Putative archaeal flagellar protein D/E MSM0137 2 COG5651 PPE-repeat proteins MSM1586, MSM1590 Cytoskeleton (Z) 1 COG5023 Tubulin MSM1794 Intracellular Trafficking and Secretion (U) 1 COG0201 Preprotein translocase subunit SecY MSM0738 1 COG0541 Signal recognition particle GTPase MSM1360 1 COG0552 Signal recognition particle GTPase MSM0701 2 COG0681 Signal peptidase I MSM0232, MSM1232 3 COG0811 Biopolymer transport proteins MSM0978, MSM1401, MSM1718 1 COG0848 Biopolymer transport protein MSM0977 1 COG1400 Signal recognition particle 19 kDa protein MSM1501 1 COG2443 Preprotein translocase subunit Sss1 MSM0625 2 COG3210 Large exoproteins involved in heme utilization or MSM0461, MSM1398 adhesion 1 COG4023 Preprotein translocase subunit Sec61beta MSM1363 1 COG4962 Flp pilus assembly protein, ATPase CpaF MSM0597 2 COG4965 Flp pilus assembly protein TadB MSM0471, MSM0596 Post-translational Modification, Protein Turnover, Chaperones (O) 1 COG0068 Hydrogenase maturation factor MSM1106 1 COG0071 Molecular chaperone (small heat shock protein) MSM0870 1 COG0225 Peptide methionine sulfoxide reductase MSM0582 1 COG0298 Hydrogenase maturation factor MSM0636 1 COG0309 Hydrogenase maturation factor MSM1492 1 COG0396 ABC-type transport system involved in Fe—S cluster MSM1003 assembly, ATPase component 1 COG0409 Hydrogenase maturation factor MSM0945 1 COG0443 Molecular chaperone MSM1109 3 COG0459 Chaperonin GroEL (HSP60 family) MSM0220, MSM0826, MSM1533 1 COG0464 ATPases of the AAA+ class MSM0642 1 COG0484 DnaJ-class molecular chaperone with C-terminal Zn MSM1110 finger domain 1 COG0492 Thioredoxin reductase MSM0340 2 COG0501 Zn-dependent protease with chaperone function MSM1174, MSM1203 1 COG0533 Metal-dependent proteases with possible chaperone MSM1198 activity 1 COG0576 Molecular chaperone GrpE (heat shock protein) MSM1108 1 COG0602 Organic radical activating enzymes MSM1055 2 COG0638 20S proteasome, alpha and beta subunits MSM0245, MSM1037 1 COG0652 Peptidyl-prolyl cis-trans isomerase (rotamase) - MSM1367 cyclophilin family 1 COG0719 ABC-type transport system involved in Fe—S cluster MSM1002 assembly, permease component 1 COG0785 Cytochrome c biogenesis protein MSM0549 3 COG0826 Collagenase and related proteases MSM0522, MSM0523, MSM1705 1 COG1047 FKBP-type peptidyl-prolyl cis-trans isomerases 2 MSM0930 1 COG1067 Predicted ATP-dependent protease MSM1569 3 COG1180 Pyruvate-formate lyase-activating enzyme MSM0538, MSM0652, MSM1284 1 COG1222 ATP-dependent 26S proteasome regulatory subunit MSM0354 1 COG1382 Prefoldin, chaperonin cofactor MSM1634 1 COG1397 ADP-ribosylglycohydrolase MSM1572 1 COG1730 Predicted prefoldin, molecular chaperone implicated MSM0702 in de novo protein folding 1 COG1899 Deoxyhypusine synthase MSM1615 1 COG1973 Hydrogenase maturation factor MSM1158 1 COG2143 Thioredoxin-related protein MSM0550 1 COG4070 Predicted peptidyl-prolyl cis-trans isomerase MSM0813 (rotamase), cyclophilin family 1 COG4930 Predicted ATP-dependent Lon-type protease MSM1754 Energy Production and Conversion (C) 1 COG0045 Succinyl-CoA synthetase, beta subunit MSM0924 1 COG0074 Succinyl-CoA synthetase, alpha subunit MSM0228 1 COG0221 Inorganic pyrophosphatase MSM0198 1 COG0240 Glycerol-3-phosphate dehydrogenase MSM1540 2 COG0243 Anaerobic dehydrogenases, typically selenocysteine- MSM1404, MSM1463 containing 1 COG0247 Fe—S oxidoreductase MSM1625 1 COG0371 Glycerol dehydrogenase and related enzymes MSM0286 1 COG0372 Citrate synthase MSM0446 2 COG0426 Uncharacterized flavoproteins MSM0222, MSM1349 1 COG0479 Succinate dehydrogenase/fumarate reductase, Fe—S MSM0393 protein subunit 1 COG0636 F0F1-type ATP synthase, subunit MSM0439 c/Archaeal/vacuolar-type H+-ATPase, subunit K 1 COG0644 Dehydrogenases (flavoproteins) MSM1701 2 COG0650 Formate hydrogenlyase subunit 4 MSM0317, MSM1062 3 COG0674 Pyruvate:ferredoxin oxidoreductase and related 2- MSM0332, MSM0559, oxoacid:ferredoxin oxidoreductases, alpha subunit MSM0927 1 COG0680 Ni,Fe-hydrogenase maturation factor MSM1123 3 COG0716 Flavodoxins MSM0062, MSM0503, MSM0861 1 COG0731 Fe—S oxidoreductases MSM0922 4 COG0778 Nitroreductase MSM0445, MSM1293, MSM1574, MSM1722 1 COG0822 NifU homolog involved in Fe—S cluster formation MSM0263 1 COG1012 NAD-dependent aldehyde dehydrogenases MSM0467 3 COG1013 Pyruvate:ferredoxin oxidoreductase and related 2- MSM0333, MSM0560, oxoacid:ferredoxin oxidoreductases, beta subunit MSM0926 3 COG1014 Pyruvate:ferredoxin oxidoreductase and related 2- MSM0391, MSM0557, oxoacid:ferredoxin oxidoreductases, gamma subunit MSM0925 1 COG1029 Formylmethanofuran dehydrogenase subunit B MSM1412 2 COG1032 Fe—S oxidoreductase MSM0696, MSM0787 4 COG1035 Coenzyme F420-reducing hydrogenase, beta subunit MSM0135, MSM1121, MSM1405, MSM1462 1 COG1036 Archaeal flavoproteins MSM1338 1 COG1042 Acyl-CoA synthetase (NDP forming) MSM1471 1 COG1053 Succinate dehydrogenase/fumarate reductase, MSM1258 flavoprotein subunit 1 COG1139 Uncharacterized conserved protein containing a MSM1626 ferredoxin-like domain 2 COG1142 Fe—S-cluster-containing hydrogenase components 2 MSM0561, MSM0562 2 COG1143 Formate hydrogenlyase subunit 6/NADH:ubiquinone MSM0998, MSM1065 oxidoreductase 23 kD subunit (chain I) 1 COG1144 Pyruvate:ferredoxin oxidoreductase and related 2- MSM0558 oxoacid:ferredoxin oxidoreductases, delta subunit 12  COG1145 Ferredoxin MSM0136, MSM0306, MSM0310, MSM0311, MSM0395, MSM0579, MSM0783, MSM0784, MSM1066, MSM1409, MSM1410, MSM1700 5 COG1146 Ferredoxin MSM0085, MSM0209, MSM0331, MSM0928, MSM1408 2 COG1148 Heterodisulfide reductase, subunit A and related MSM0082, MSM1336 polyferredoxins 2 COG1150 Heterodisulfide reductase, subunit C MSM0084, MSM0796 1 COG1151 6Fe—6S prismane cluster-containing protein MSM1446 1 COG1153 Formylmethanofuran dehydrogenase subunit D MSM1411 1 COG1155 Archaeal/vacuolar-type H+-ATPase subunit A MSM0435 1 COG1156 Archaeal/vacuolar-type H+-ATPase subunit B MSM0434 1 COG1229 Formylmethanofuran dehydrogenase subunit A MSM1413 1 COG1249 Pyruvate/2-oxoglutarate dehydrogenase complex, MSM0637 dihydrolipoamide dehydrogenase (E3) component, and related enzymes 1 COG1269 Archaeal/vacuolar-type H+-ATPase subunit I MSM0440 1 COG1304 L-lactate dehydrogenase (FMN-dependent) and MSM1441 related alpha-hydroxy acid dehydrogenases 1 COG1390 Archaeal/vacuolar-type H+-ATPase subunit E MSM0438 1 COG1394 Archaeal/vacuolar-type H+-ATPase subunit D MSM0433 2 COG1413 FOG: HEAT repeat MSM0372, MSM0501 1 COG1436 Archaeal/vacuolar-type H+-ATPase subunit F MSM0436 2 COG1526 Uncharacterized protein required for formate MSM0295, MSM1392 dehydrogenase activity 1 COG1527 Archaeal/vacuolar-type H+-ATPase subunit C MSM0437 2 COG1592 Rubrerythrin MSM1348, MSM1733 1 COG1600 Uncharacterized Fe—S protein MSM0609 1 COG1625 Fe—S oxidoreductase, related to NifB/MoaA family MSM1020 2 COG1773 Rubredoxin MSM0187, MSM0188 2 COG1838 Tartrate dehydratase beta subunit/Fumarate MSM0769, MSM0929 hydratase class I, C-terminal domain 2 COG1908 Coenzyme F420-reducing hydrogenase, delta subunit MSM1001, MSM1461 2 COG1941 Coenzyme F420-reducing hydrogenase, gamma MSM1000, MSM1122 subunit 2 COG1951 Tartrate dehydratase alpha subunit/Fumarate MSM0447, MSM0563 hydratase class I, N-terminal domain 1 COG2033 Desulfoferrodoxin MSM0262 2 COG2037 Formylmethanofuran:tetrahydromethanopterin MSM0308, MSM1092 formyltransferase 2 COG2048 Heterodisulfide reductase, subunit B MSM0083, MSM0795 1 COG2055 Malate/L-lactate dehydrogenases MSM1040 1 COG2141 Coenzyme F420-dependent N5,N10-methylene MSM0542 tetrahydromethanopterin reductase and related flavin- dependent oxidoreductases 1 COG2191 Formylmethanofuran dehydrogenase subunit E MSM1396 1 COG2218 Formylmethanofuran dehydrogenase subunit C MSM1414 1 COG2710 Nitrogenase molybdenum-iron protein, alpha and beta MSM1160 chains 1 COG2811 Archaeal/vacuolar-type H+-ATPase subunit H MSM0441 2 COG3259 Coenzyme F420-reducing hydrogenase, alpha subunit MSM0999, MSM1124 1 COG3260 Ni,Fe-hydrogenase III small subunit MSM1064 1 COG3261 Ni,Fe-hydrogenase III large subunit MSM1063 2 COG4231 Indolepyruvate ferredoxin oxidoreductase, alpha and MSM0392, MSM1460 beta subunits 1 COG5016 Pyruvate/oxaloacetate carboxyltransferase MSM0939 Carbohydrate Transport and Metabolism (G) 1 COG0057 Glyceraldehyde-3-phosphate MSM0962 dehydrogenase/erythrose-4-phosphate dehydrogenase 1 COG0063 Predicted sugar kinase MSM1091 1 COG0120 Ribose 5-phosphate isomerase MSM0284 1 COG0126 3-phosphoglycerate kinase MSM0918 1 COG0148 Enolase MSM1435 1 COG0149 Triosephosphate isomerase MSM0919 1 COG0235 Ribulose-5-phosphate 4-epimerase and related MSM1270 epimerases and aldolases 1 COG0483 Archaeal fructose-1,6-bisphosphatase and related MSM0879 enzymes of inositol monophosphatase family 3 COG0524 Sugar kinases, ribokinase family MSM0307, MSM1389, MSM1693 2 COG0574 Phosphoenolpyruvate synthase/pyruvate phosphate MSM0823, MSM0988 dikinase 1 COG0580 Glycerol uptake facilitator and related permeases MSM1085 (Major Intrinsic Protein Family) 2 COG1082 Sugar phosphate isomerases/epimerases MSM1184, MSM1251 2 COG1109 Phosphomannomutase MSM0648, MSM0656 1 COG1363 Cellulase M and related proteins MSM0134 1 COG1830 DhnA-type fructose-1,6-bisphosphate aldolase and MSM0056 related enzymes 1 COG1980 Archaeal fructose 1,6-bisphosphatase MSM0615 2 COG2074 2-phosphoglycerate kinase MSM0408, MSM0791 2 COG2730 Endoglucanase MSM1051, MSM1125 2 COG2814 Arabinose efflux permease MSM1459, MSM1465 2 COG3635 Predicted phosphoglycerate mutase, AP superfamily MSM0153, MSM0657 1 COG5297 Cellobiohydrolase A (1,4-beta-cellobiosidase A) MSM0958 Amino Acid Transport and Metabolism (E) 1 COG0002 Acetylglutamate semialdehyde dehydrogenase MSM0860 1 COG0006 Xaa-Pro aminopeptidase MSM0472 1 COG0019 Diaminopimelate decarboxylase MSM1371 1 COG0031 Cysteine synthase MSM0271 1 COG0040 ATP phosphoribosyltransferase MSM1261 2 COG0065 3-isopropylmalate dehydratase large subunit MSM0723, MSM1300 2 COG0066 3-isopropylmalate dehydratase small subunit MSM0847, MSM1299 1 COG0067 Glutamate synthase domain 1 MSM0370 2 COG0069 Glutamate synthase domain 2 MSM0027, MSM0368 1 COG0070 Glutamate synthase domain 3 MSM0369 2 COG0075 Serine-pyruvate aminotransferase/archaeal aspartate MSM0677, MSM1513 aminotransferase 1 COG0076 Glutamate decarboxylase and related PLP-dependent MSM0987 proteins 1 COG0077 Prephenate dehydratase MSM1052 1 COG0078 Ornithine carbamoyltransferase MSM1226 2 COG0079 Histidinol-phosphate/aromatic aminotransferase and MSM0653, MSM1516 cobyric acid decarboxylase 1 COG0082 Chorismate synthase MSM1474 1 COG0106 Phosphoribosylformimino-5-aminoimidazole MSM0858 carboxamide ribonucleotide (ProFAR) isomerase 1 COG0107 Imidazoleglycerol-phosphate synthase MSM1364 1 COG0112 Glycine/serine hydroxymethyltransferase MSM1337 1 COG0118 Glutamine amidotransferase MSM1159 3 COG0119 Isopropylmalate/homocitrate/citramalate synthases MSM0350, MSM0722, MSM1246 1 COG0128 5-enolpyruvylshikimate-3-phosphate synthase MSM0273 1 COG0131 Imidazoleglycerol-phosphate dehydratase MSM1206 1 COG0133 Tryptophan synthase beta chain MSM1142 1 COG0134 Indole-3-glycerol phosphate synthase MSM1143 1 COG0136 Aspartate-semialdehyde dehydrogenase MSM0829 1 COG0137 Argininosuccinate synthase MSM1084 1 COG0139 Phosphoribosyl-AMP cyclohydrolase MSM1182 1 COG0140 Phosphoribosyl-ATP pyrophosphohydrolase MSM1103 1 COG0141 Histidinol dehydrogenase MSM1238 1 COG0165 Argininosuccinate lyase MSM0192 1 COG0169 Shikimate 5-dehydrogenase MSM1179 1 COG0174 Glutamine synthetase MSM1418 1 COG0253 Diaminopimelate epimerase MSM1372 1 COG0287 Prephenate dehydrogenase MSM0641 1 COG0289 Dihydrodipicolinate reductase MSM0830 1 COG0334 Glutamate dehydrogenase/leucine dehydrogenase MSM0888 1 COG0345 Pyrroline-5-carboxylate reductase MSM0089 1 COG0346 Lactoylglutathione lyase and related lyases MSM1366 1 COG0347 Nitrogen regulatory protein PII MSM0233 1 COG0367 Asparagine synthase (glutamine-hydrolyzing) MSM0160 3 COG0436 Aspartate/tyrosine/aromatic aminotransferase MSM0610, MSM0788, MSM1455 1 COG0440 Acetolactate synthase, small (regulatory) subunit MSM1224 1 COG0460 Homoserine dehydrogenase MSM0154 1 COG0498 Threonine synthase MSM0214 1 COG0527 Aspartokinases MSM0832 1 COG0547 Anthranilate phosphoribosyltransferase MSM1144 1 COG0548 Acetylglutamate kinase MSM0375 1 COG0560 Phosphoserine phosphatase MSM0719 1 COG0620 Methionine synthase II (cobalamin-independent) MSM0102 1 COG0710 3-dehydroquinate dehydratase MSM0231 1 COG0747 ABC-type dipeptide transport system, periplasmic MSM0300 component 1 COG0765 ABC-type amino acid transport system, permease MSM0806 component 1 COG1045 Serine acetyltransferase MSM0270 1 COG1104 Cysteine sulfinate desulfinase/cysteine desulfurase MSM0264 and related enzymes 1 COG1125 ABC-type proline/glycine betaine transport systems, MSM0990 ATPase components 1 COG1126 ABC-type polar amino acid transport system, ATPase MSM0805 component 1 COG1168 Bifunctional PLP-dependent enzyme with beta- MSM0044 cystathionase and maltose regulon repressor activities 1 COG1174 ABC-type proline/glycine betaine transport systems, MSM0991 permease component 2 COG1305 Transglutaminase-like enzymes, putative cysteine MSM0219, MSM0786 proteases 1 COG1465 Predicted alternative 3-dehydroquinate synthase MSM0055 1 COG1605 Chorismate mutase MSM0834 1 COG1812 Archaeal S-adenosylmethionine synthetase MSM1340 1 COG1921 Selenocysteine synthase [seryl-tRNASer selenium MSM0767 transferase] 1 COG2021 Homoserine acetyltransferase MSM0496 1 COG2061 ACT-domain-containing protein, predicted allosteric MSM0155 regulator of homoserine dehydrogenase 1 COG2303 Choline dehydrogenase and related flavoproteins MSM0865 1 COG2423 Predicted ornithine cyclodeaminase, mu-crystallin MSM1517 homolog 1 COG2856 Predicted Zn peptidase MSM1529 2 COG2873 O-acetylhomoserine sulfhydrylase MSM0174, MSM0265 1 COG4992 Ornithine/acetylornithine aminotransferase MSM1368 Nucleic Acid Transport and Metabolism (F) 1 COG0005 Purine nucleoside phosphorylase MSM0665 1 COG0015 Adenylosuccinate lyase MSM1151 1 COG0034 Glutamine phosphoribosylpyrophosphate MSM1704 amidotransferase 1 COG0035 Uracil phosphoribosyltransferase MSM0398 1 COG0041 Phosphoribosylcarboxyaminoimidazole (NCAIR) MSM1287 mutase 1 COG0044 Dihydroorotase and related cyclic amidohydrolases MSM0997 1 COG0046 Phosphoribosylformylglycinamidine (FGAM) synthase, MSM1342 synthetase domain 1 COG0047 Phosphoribosylformylglycinamidine (FGAM) synthase, MSM1549 glutamine amidotransferase domain 1 COG0104 Adenylosuccinate synthase MSM1468 1 COG0105 Nucleoside diphosphate kinase MSM0203 2 COG0125 Thymidylate kinase MSM0077, MSM0520 1 COG0127 Xanthosine triphosphate pyrophosphatase MSM1195 1 COG0150 Phosphoribosylaminoimidazole (AIR) synthetase MSM1039 1 COG0151 Phosphoribosylamine-glycine ligase MSM1227 1 COG0152 Phosphoribosylaminoimidazolesuccinocarboxamide MSM1547 (SAICAR) synthase 1 COG0167 Dihydroorotate dehydrogenase MSM1044 1 COG0207 Thymidylate synthase MSM1734 1 COG0274 Deoxyribose-phosphate aldolase MSM0843 1 COG0284 Orotidine-5′-phosphate decarboxylase MSM1617 1 COG0461 Orotate phosphoribosyltransferase MSM0821 1 COG0503 Adenine/guanine phosphoribosyltransferases and MSM1359 related PRPP-binding proteins 1 COG0504 CTP synthase (UTP-ammonia lyase) MSM0147 1 COG0516 IMP dehydrogenase/GMP reductase MSM1629 1 COG0518 GMP synthase - Glutamine amidotransferase domain MSM0343 1 COG0519 GMP synthase, PP-ATPase domain/subunit MSM0345 1 COG0528 Uridylate kinase MSM0415 1 COG0540 Aspartate carbamoyltransferase, catalytic chain MSM1263 2 COG0717 Deoxycytidine deaminase MSM0402, MSM0687 1 COG0856 Orotate phosphoribosyltransferase homologs MSM0883 1 COG1001 Adenine deaminase MSM0874 1 COG1051 ADP-ribose pyrophosphatase MSM1355 1 COG1102 Cytidylate kinase MSM0734 1 COG1328 Oxygen-sensitive ribonucleoside-triphosphate MSM1383 reductase 1 COG1437 Adenylate cyclase, class 2 (thermophilic) MSM0721 1 COG1781 Aspartate carbamoyltransferase, regulatory subunit MSM0862 1 COG1828 Phosphoribosylformylglycinamidine (FGAM) synthase, MSM1548 PurS component 1 COG1936 Predicted nucleotide kinase (related to CMP and AMP MSM0713 kinases) 1 COG2019 Archaeal adenylate kinase MSM0737 1 COG2233 Xanthine/uracil permeases MSM0397 1 COG3363 Archaeal IMP cyclohydrolase MSM0976 Coenzyme Transport and Metabolism (H) 1 COG0001 Glutamate-1-semialdehyde aminotransferase MSM1233 1 COG0007 Uroporphyrinogen-III methylase MSM1550 1 COG0043 3-polyprenyl-4-hydroxybenzoate decarboxylase and MSM1286 related decarboxylases 1 COG0054 Riboflavin synthase beta-chain MSM1296 1 COG0108 3,4-dihydroxy-2-butanone 4-phosphate synthase MSM1256 1 COG0113 Delta-aminolevulinic acid dehydratase MSM1476 1 COG0142 Geranylgeranyl pyrophosphate synthase MSM1443 1 COG0157 Nicotinate-nucleotide pyrophosphorylase MSM0491 1 COG0163 3-polyprenyl-4-hydroxybenzoate decarboxylase MSM0237 1 COG0171 NAD synthase MSM1171 1 COG0181 Porphobilinogen deaminase MSM0881 1 COG0237 Dephospho-CoA kinase MSM0141 1 COG0294 Dihydropteroate synthase and related enzymes MSM0556 1 COG0301 Thiamine biosynthesis ATP pyrophosphatase MSM0617 2 COG0303 Molybdopterin biosynthesis enzyme MSM0950, MSM1343 1 COG0311 Predicted glutamine amidotransferase involved in MSM0371 pyridoxine biosynthesis 1 COG0314 Molybdopterin converting factor, large subunit MSM0130 1 COG0315 Molybdenum cofactor biosynthesis enzyme MSM1362 1 COG0340 Biotin-(acetyl-CoA carboxylase) ligase MSM0766 1 COG0351 Hydroxymethylpyrimidine/phosphomethylpyrimidine MSM0289 kinase 1 COG0352 Thiamine monophosphate synthase MSM0917 1 COG0373 Glutamyl-tRNA reductase MSM0967 1 COG0379 Quinolinate synthase MSM0494 1 COG0382 4-hydroxybenzoate polyprenyltransferase and related MSM0941 prenyltransferases 1 COG0407 Uroporphyrinogen-III decarboxylase MSM0518 2 COG0422 Thiamine biosynthesis protein ThiC MSM0644, MSM1388 2 COG0452 Phosphopantothenoylcysteine MSM1048, MSM1049 synthetase/decarboxylase 1 COG0476 Dinucleotide-utilizing enzymes involved in MSM0729 molybdopterin and thiamine biosynthesis family 2 1 COG0499 S-adenosylhomocysteine hydrolase MSM0727 2 COG0502 Biotin synthase and related enzymes MSM0573, MSM1099 1 COG0521 Molybdopterin biosynthesis enzymes MSM0820 1 COG0611 Thiamine monophosphate kinase MSM1283 1 COG0684 Demethylmenaquinone methyltransferase MSM0426 1 COG0720 6-pyruvoyl-tetrahydropterin synthase MSM1056 1 COG0746 Molybdopterin-guanine dinucleotide biosynthesis MSM0240 protein A 1 COG1010 Precorrin-3B methylase MSM1273 1 COG1056 Nicotinamide mononucleotide adenylyltransferase MSM0129 1 COG1270 Cobalamin biosynthesis protein CobD/CbiB MSM1266 2 COG1429 Cobalamin biosynthesis protein CobN and related Mg- MSM1117, MSM1715 chelatases 1 COG1488 Nicotinic acid phosphoribosyltransferase MSM1792 2 COG1492 Cobyric acid synthase MSM1254, MSM1565 2 COG1541 Coenzyme F390 synthetase MSM0387, MSM1714 1 COG1587 Uroporphyrinogen-III synthase MSM1504 1 COG1648 Siroheme synthase (precorrin-2 oxidase/ferrochelatase MSM0968 domain) 1 COG1731 Archaeal riboflavin synthase MSM1622 1 COG1763 Molybdopterin-guanine dinucleotide biosynthesis MSM1407 protein 1 COG1767 Triphosphoribosyl-dephospho-CoA synthetase MSM1477 1 COG1797 Cobyrinic acid a,c-diamide synthase MSM1215 1 COG1893 Ketopantoate reductase MSM0033 2 COG1962 Tetrahydromethanopterin S-methyltransferase, subunit H MSM0627, MSM1007 1 COG1985 Pyrimidine reductase, riboflavin biosynthesis MSM0065 1 COG2038 NaMN:DMB phosphoribosyltransferase MSM1200 1 COG2073 Cobalamin biosynthesis protein CbiG MSM1267 1 COG2082 Precorrin isomerase MSM1234 1 COG2099 Precorrin-6x reductase MSM0896 1 COG2104 Sulfur transfer protein involved in thiamine MSM0552 biosynthesis 1 COG2145 Hydroxyethylthiazole kinase, sugar kinase family MSM0916 3 COG2226 Methylase involved in ubiquinone/menaquinone MSM1448, MSM1558, biosynthesis MSM1564 1 COG2241 Precorrin-6B methylase 1 MSM1167 1 COG2242 Precorrin-6B methylase 2 MSM0238 1 COG2243 Precorrin-2 methylase MSM1351 1 COG2266 GTP:adenosylcobinamide-phosphate MSM1005 guanylyltransferase 1 COG2875 Precorrin-4 methylase MSM0101 1 COG2896 Molybdenum cofactor biosynthesis enzyme MSM1406 1 COG3161 4-hydroxybenzoate synthetase (chorismate lyase) MSM0724 1 COG3252 Methenyltetrahydromethanopterin cyclohydrolase MSM1723 2 COG4054 Methyl coenzyme M reductase, beta subunit MSM0905, MSM1019 2 COG4055 Methyl coenzyme M reductase, subunit D MSM0904, MSM1018 1 COG4056 Methyl coenzyme M reductase, subunit C MSM1017 2 COG4057 Methyl coenzyme M reductase, gamma subunit MSM0903, MSM1016 2 COG4058 Methyl coenzyme M reductase, alpha subunit MSM0902, MSM1015 1 COG4059 Tetrahydromethanopterin S-methyltransferase, MSM1014 subunit E 1 COG4060 Tetrahydromethanopterin S-methyltransferase, MSM1013 subunit D 1 COG4061 Tetrahydromethanopterin S-methyltransferase, MSM1012 subunit C 1 COG4062 Tetrahydromethanopterin S-methyltransferase, MSM1011 subunit B 1 COG4063 Tetrahydromethanopterin S-methyltransferase, MSM1010 subunit A 1 COG4064 Tetrahydromethanopterin S-methyltransferase, MSM1008 subunit G 1 COG4218 Tetrahydromethanopterin S-methyltransferase, MSM1009 subunit F Lipid Transport and Metabolism (I) 1 COG0020 Undecaprenyl pyrophosphate synthase MSM0096 1 COG0170 Dolichol kinase MSM0078 1 COG0183 Acetyl-CoA acetyltransferase MSM1562 1 COG0365 Acyl-coenzyme A synthetases/AMP-(fatty) acid MSM0330 ligases 1 COG0439 Biotin carboxylase MSM0765 2 COG0558 Phosphatidylglycerophosphate synthase MSM0613, MSM1706 1 COG0575 CDP-diglyceride synthetase MSM0850 1 COG1183 Phosphatidylserine synthase MSM0982 2 COG1211 4-diphosphocytidyl-2-methyl-D-erithritol synthase MSM0377, MSM1542 1 COG1250 3-hydroxyacyl-CoA dehydrogenase MSM0965 1 COG1257 Hydroxymethylglutaryl-CoA reductase MSM0227 1 COG1260 Myo-inositol-1-phosphate synthase MSM0940 1 COG1267 Phosphatidylglycerophosphatase A and related MSM0934 proteins 1 COG1577 Mevalonate kinase MSM1439 1 COG1924 Activator of 2-hydroxyglutaryl-CoA dehydratase MSM0810 (HSP70-class ATPase domain) 1 COG2084 MSM0548 1 COG3425 3-hydroxy-3-methylglutaryl CoA synthase MSM1561 Inorganic Ion Transport and Metabolism (P) 1 COG0003 Oxyanion-translocating ATPase MSM1170 1 COG0004 Ammonia permease MSM0234 1 COG0038 Chloride channel protein EriC MSM1721 1 COG0053 Predicted Co/Zn/Cd cation transporters MSM0789 1 COG0168 Trk-type K+ transport systems, membrane MSM1095 components 1 COG0226 ABC-type phosphate transport system, periplasmic MSM0568 component 1 COG0288 Carbonic anhydrase MSM1223 4 COG0310 ABC-type Co2+ transport system, permease MSM0583, MSM0584, component MSM1488, MSM1618 1 COG0370 Fe2+ transport system protein B MSM0589 1 COG0474 Cation transport ATPase MSM0895 1 COG0475 Kef-type K+ transport systems, membrane MSM1186 components 1 COG0530 Ca2+/Na+ antiporter MSM1027 1 COG0569 K+ transport systems, NAD-binding component MSM1096 1 COG0573 ABC-type phosphate transport system, permease MSM0567 component 1 COG0581 ABC-type phosphate transport system, permease MSM0566 component 1 COG0600 ABC-type nitrate/sulfonate/bicarbonate transport MSM0291 system, permease component 1 COG0609 ABC-type Fe3+-siderophore transport system, MSM1394 permease component 1 COG0614 ABC-type Fe3+-hydroxamate transport system, MSM1393 periplasmic component 3 COG0619 ABC-type cobalt transport system, permease MSM0585, MSM0771, component CbiQ and related transporters MSM1620 2 COG0704 Phosphate uptake regulator MSM0564, MSM0569 1 COG0715 ABC-type nitrate/sulfonate/bicarbonate transport MSM1469 systems, periplasmic components 1 COG0725 ABC-type molybdate transport system, periplasmic MSM1609 component 1 COG0798 Arsenite efflux pump ACR3 and related permeases MSM1078 1 COG0855 Polyphosphate kinase MSM1424 1 COG1006 Multisubunit Na+/H+ antiporter, MnhC subunit MSM1072 1 COG1116 ABC-type nitrate/sulfonate/bicarbonate transport MSM0290 system, ATPase component 1 COG1117 ABC-type phosphate transport system, ATPase MSM0565 component 1 COG1118 ABC-type sulfate/molybdate transport systems, MSM1611 ATPase component 2 COG1122 ABC-type cobalt transport system, ATPase MSM0586, MSM1621 component 1 COG1230 Co/Zn/Cd efflux system component MSM1639 1 COG1320 Multisubunit Na+/H+ antiporter, MnhG subunit MSM1074 1 COG1348 Nitrogenase subunit NifH (ATPase) MSM1707 1 COG1528 Ferritin-like protein MSM1712 1 COG1563 Predicted subunit of the Multisubunit Na+/H+ MSM1073 antiporter 1 COG1824 Permease, similar to cation transporters MSM1275 1 COG1863 Multisubunit Na+/H+ antiporter, MnhE subunit MSM1076 1 COG1918 Fe2+ transport system protein A MSM0588 1 COG1930 ABC-type cobalt transport system, periplasmic MSM1619 component 2 COG2111 Multisubunit Na+/H+ antiporter, MnhB subunit MSM1068, MSM1069 1 COG2116 Formate/nitrite family of transporters MSM1403 1 COG2212 Multisubunit Na+/H+ antiporter, MnhF subunit MSM1075 4 COG2217 Cation transport ATPase MSM0293, MSM0960, MSM1127, MSM1153 1 COG2608 Copper chaperone MSM0961 1 COG3263 NhaP-type Na+/H+ and K+/H+ antiporters with a MSM0618 unique C-terminal domain 1 COG3420 Nitrous oxidase accessory protein MSM1397 1 COG4149 ABC-type molybdate transport system, permease MSM1610 component Secondary Metabolites Biosynthesis, Transport and Catabolism (Q) 1 COG1228 Imidazolonepropionase and related amidohydrolases MSM1154 General Function Prediction Only (R) 2 COG0110 Acetyltransferase (isoleucine patch superfamily) MSM0189, MSM1600 2 COG0312 Predicted Zn-dependent proteases and their MSM0866, MSM0947 inactivated homologs 1 COG0375 Zn finger protein HypA/HybF (possibly regulating MSM0108 hydrogenase expression) 1 COG0388 Predicted amidohydrolase MSM0500 1 COG0433 Predicted ATPase MSM0122 1 COG0446 Uncharacterized NAD(FAD)-dependent MSM0046 dehydrogenases 2 COG0456 Acetyltransferases MSM0893, MSM1104 11  COG0457 FOG: TPR repeat MSM0530, MSM0651, MSM0914, MSM1449, MSM1451, MSM1740, MSM1766, MSM1776, MSM1786, MSM1787, MSM1788 2 COG0491 Zn-dependent hydrolases, including glyoxylases MSM0421, MSM1097 1 COG0496 Predicted acid phosphatase MSM1218 2 COG0517 FOG: CBS domain MSM0175, MSM1102 4 COG0535 Predicted Fe—S oxidoreductases MSM0663, MSM0808, MSM1301, MSM1497 1 COG0561 Predicted hydrolases of the HAD superfamily MSM0946 1 COG0595 Predicted hydrolase of the metallo-beta-lactamase MSM1442 superfamily 1 COG0603 Predicted PP-loop superfamily ATPase MSM0936 1 COG0613 Predicted metal-dependent phosphoesterases (PHP MSM1244 family) 1 COG0622 Predicted phosphoesterase MSM0507 1 COG0627 Predicted esterase MSM0149 1 COG0628 Predicted permease MSM1042 1 COG0641 Arylsulfatase regulator (Fe—S oxidoreductase) MSM1606 5 COG0655 Multimeric flavodoxin WrbA MSM0267, MSM0664, MSM0923, MSM1209, MSM1727 1 COG0661 Predicted unusual protein kinase MSM0525 1 COG0663 Carbonic anhydrases/acetyltransferases, isoleucine MSM0654 patch superfamily 1 COG0666 FOG: Ankyrin repeat MSM0266 1 COG0673 Predicted dehydrogenases and related proteins MSM0882 1 COG0679 Predicted permeases MSM1334 1 COG0714 MoxR-like ATPases MSM0555 1 COG0730 Predicted permeases MSM0420 3 COG0733 Na+-dependent transporters of the SNF family MSM0699, MSM1531, MSM1532 1 COG0824 Predicted thioesterase MSM0133 1 COG1011 Predicted hydrolase (HAD superfamily) MSM1480 1 COG1019 Predicted nucleotidyltransferase MSM0785 1 COG1078 HD superfamily phosphohydrolases MSM0236 1 COG1084 Predicted GTPase MSM0869 1 COG1094 Predicted RNA-binding protein (contains KH domains) MSM0954 1 COG1099 Predicted metal-dependent hydrolases with the TIM- MSM0405 barrel fold 3 COG1123 ATPase components of various ABC-type transport MSM0770, MSM0971, systems, contain duplicated ATPase MSM1698 2 COG1163 Predicted GTPase MSM0714, MSM0715 1 COG1201 Lhr-like helicases MSM0502 1 COG1202 Superfamily II helicase, archaea-specific MSM1583 1 COG1203 Predicted helicases MSM0166 1 COG1204 Superfamily II helicase MSM0839 1 COG1205 Distinct helicase family with a unique C-terminal MSM0112 domain including a metal-binding cysteine cluster 5 COG1216 Predicted glycosyltransferases MSM1321, MSM1329, MSM1330, MSM1503, MSM1507 1 COG1223 Predicted ATPase (AAA+ superfamily) MSM0966 1 COG1234 Metal-dependent hydrolases of the beta-lactamase MSM0492 superfamily III 1 COG1235 Metal-dependent hydrolases of the beta-lactamase MSM1473 superfamily I 1 COG1244 Predicted Fe—S oxidoreductase MSM0544 1 COG1245 Predicted ATPase, RNase L inhibitor (RLI) homolog MSM0607 1 COG1253 Hemolysins and related proteins containing CBS MSM1026 domains 4 COG1266 Predicted metal-dependent membrane protease MSM0292, MSM0803, MSM1148, MSM1180 1 COG1268 Uncharacterized conserved protein MSM0429 2 COG1277 ABC-type transport system involved in multi-copper MSM0594, MSM0595 enzyme maturation, permease component 1 COG1287 Uncharacterized membrane protein, required for N- MSM0716 linked glycosylation 1 COG1310 Predicted metal-dependent protease of the MSM0462 PAD1/JAB1 superfamily 2 COG1323 Predicted nucleotidyltransferase MSM0547, MSM0994 1 COG1326 Uncharacterized archaeal Zn-finger protein MSM0846 2 COG1342 Predicted DNA-binding proteins MSM0207, MSM0208 1 COG1350 Predicted alternative tryptophan synthase beta- MSM1242 subunit (paralog of TrpB) 1 COG1355 Predicted dioxygenase MSM1438 1 COG1365 Predicted ATPase (PP-loop superfamily) MSM0190 9 COG1373 Predicted ATPase (AAA+ superfamily) MSM0061, MSM0280, MSM0680, MSM1197, MSM1278, MSM1527, MSM1789, MSM1790, MSM1795 1 COG1402 Uncharacterized protein, putative amidase MSM0184 2 COG1408 Predicted phosphohydrolases MSM0964, MSM1165 1 COG1409 Predicted phosphohydrolases MSM0383 1 COG1411 Uncharacterized protein related to proFAR isomerase MSM1636 (HisA) 1 COG1412 Uncharacterized proteins of PilT N-term./Vapc MSM0199 superfamily 1 COG1418 Predicted HD superfamily hydrolase MSM0632 1 COG1439 Predicted nucleic acid-binding protein, consists of a MSM0816 PIN domain and a Znribbon module 4 COG1453 Predicted oxidoreductases of the aldo/keto reductase MSM0148, MSM0728, family MSM1450, MSM1608 1 COG1489 DNA-binding protein, stimulates sugar fermentation MSM1090 1 COG1537 Predicted RNA-binding proteins MSM0640 1 COG1545 Predicted nucleic-acid-binding protein containing a MSM1279 Zn-ribbon 2 COG1571 Predicted DNA-binding protein containing a Zn-ribbon MSM0452, MSM1295 domain 1 COG1606 ATP-utilizing enzymes of the PP-loop superfamily MSM0482 1 COG1608 Predicted archaeal kinase MSM1440 1 COG1611 Predicted Rossmann fold nucleotide-binding protein MSM0004 1 COG1634 Uncharacterized Rossmann fold enzyme MSM0672 1 COG1646 Predicted phosphate-binding enzymes, TIM-barrel MSM0124 fold 2 COG1672 Predicted ATPase (AAA+ superfamily) MSM1196, MSM1646 1 COG1691 NCAIR mutase (PurE)-related proteins MSM1105 1 COG1707 ACT domain-containing protein MSM1060 1 COG1759 ATP-utilizing enzymes of ATP-grasp superfamily MSM0506 (probably carboligases) 1 COG1779 C4-type Zn-finger protein MSM0409 1 COG1782 Predicted metal-dependent RNase, consists of a MSM1038 metallo-beta-lactamase domain and an RNA-binding KH domain 1 COG1821 Predicted ATP-utilizing enzyme (ATP-grasp MSM0852 superfamily) 1 COG1829 Predicted archaeal kinase (sugar kinase superfamily) MSM0060 1 COG1855 ATPase (PilT family) MSM1183 1 COG1878 Predicted metal-dependent hydrolase MSM0827 1 COG1907 Predicted archaeal sugar kinases MSM0848 1 COG1942 Uncharacterized protein, 4-oxalocrotonate MSM0688 tautomerase homolog 1 COG1964 Predicted Fe—S oxidoreductases MSM0849 1 COG1988 Predicted membrane-bound metal-dependent MSM1079 hydrolases 1 COG1994 Zn-dependent proteases MSM0479 2 COG2005 N-terminal domain of molybdenum-binding protein MSM0131, MSM1207 1 COG2047 Uncharacterized protein (ATP-grasp superfamily) MSM1131 1 COG2054 Uncharacterized archaeal kinase related to MSM0604 aspartokinases, uridylate kinases 1 COG2068 Uncharacterized MobA-related protein MSM0116 1 COG2079 Uncharacterized protein involved in propionate MSM0449 catabolism 1 COG2081 Predicted flavoproteins MSM1235 1 COG2085 Predicted dinucleotide-binding enzymes MSM0049 1 COG2102 Predicted ATPases of PP-loop superfamily MSM0142 1 COG2118 DNA-binding protein MSM0708 1 COG2129 Predicted phosphoesterases, related to the lcc MSM0792 protein 1 COG2150 Predicted regulator of amino acid metabolism, MSM0635 contains ACT domain 1 COG2151 Predicted metal-sulfur cluster biosynthetic enzyme MSM0634 1 COG2220 Predicted Zn-dependent hydrolases of the beta- MSM0779 lactamase fold 1 COG2232 Predicted ATP-dependent carboligase related to MSM0431 biotin carboxylase 3 COG2244 Membrane protein involved in the export of O-antigen MSM1208, MSM1559, and teichoic acid MSM1560 1 COG2252 Permeases MSM1736 1 COG2403 Predicted GTPase MSM0091 1 COG2405 Predicted nucleic acid-binding protein, contains PIN MSM1530 domain 1 COG2517 Predicted RNA-binding protein containing a C- MSM0466 terminal EMAP domain 2 COG2520 Predicted methyltransferase MSM0802, MSM1036 1 COG2522 Predicted transcriptional regulator MSM0269 3 COG3291 FOG: PKD repeat MSM0281, MSM1716, MSM1735 1 COG3442 Predicted glutamine amidotransferase MSM1138 1 COG3552 Protein containing von Willebrand factor type A MSM0554 (vWA) domain 1 COG3608 Predicted deacylase MSM1080 1 COG3894 Uncharacterized metal-binding protein MSM0517 1 COG3942 Surface antigen MSM0921 1 COG3943 Virulence protein MSM1645 1 COG4002 Predicted phosphotransacetylase MSM0095 1 COG4015 Predicted dinucleotide-utilizing enzyme of the MSM0577 ThiF/HesA family 1 COG4026 Uncharacterized protein containing TOPRIM domain, MSM1703 potential nuclease 2 COG4032 Predicted thiamine-pyrophosphate-binding protein MSM0080, MSM0081 1 COG4052 Uncharacterized protein related to methyl coenzyme MSM1021 M reductase subunit C 1 COG4076 Predicted RNA methylase MSM0363 1 COG4085 Predicted RNA-binding protein, contains TRAM MSM0647 domain 1 COG4087 Soluble P-type ATPase MSM1252 1 COG4277 Predicted DNA-binding protein with the Helix-hairpin- MSM1239 helix motif 2 COG4747 ACT domain-containing protein MSM0388, MSM1713 1 COG4801 Predicted acyltransferase MSM1385 1 COG4827 Predicted transporter MSM1717 1 COG5012 Predicted cobalamin binding protein MSM0516 3 COG5271 AAA ATPase containing von Willebrand factor type A MSM0993, MSM1240, (vWA) domain MSM1454 1 COG5362 Phage-related terminase MSM1671 1 COG5518 Bacteriophage capsid portal protein MSM1672 2 COG5643 Protein containing a metal-binding domain shared MSM1489, MSM1491 with formylmethanofuran dehydrogenase subunit E Function Unknown (S) 1 COG0011 Uncharacterized conserved protein MSM1029 2 COG0028 MSM0686, MSM1225 1 COG0059 MSM1222 1 COG0111 MSM0457 1 COG0147 MSM1146 1 COG0248 MSM1423 2 COG0318 MSM0025, MSM0374 1 COG0327 Uncharacterized conserved protein MSM0576 1 COG0378 MSM0107 1 COG0391 Uncharacterized conserved protein MSM0974 1 COG0392 Predicted integral membrane protein MSM1094 2 COG0393 Uncharacterized conserved protein MSM0418, MSM0456 1 COG0432 Uncharacterized conserved protein MSM0279 1 COG0444 MSM0303 1 COG0451 MSM0327 2 COG0458 MSM0361, MSM0488 1 COG0462 MSM1577 2 COG0473 MSM0373, MSM1298 2 COG0477 MSM0772, MSM1210 2 COG0500 MSM0028, MSM1510 1 COG0505 MSM0489 1 COG0512 MSM1145 1 COG0513 MSM1498 1 COG0543 MSM1043 1 COG0585 Uncharacterized conserved protein MSM1156 1 COG0591 MSM0386 1 COG0599 Uncharacterized homolog of gamma- MSM0296 carboxymuconolactone decarboxylase subunit 1 COG0601 MSM0301 2 COG0615 MSM0859, MSM1514 1 COG1028 MSM1731 2 COG1061 MSM0690, MSM0695 1 COG1063 MSM0376 1 COG1086 MSM1535 1 COG1120 MSM1395 1 COG1124 MSM0304 2 COG1134 MSM1326, MSM1592 1 COG1173 MSM0302 1 COG1199 MSM1352 1 COG1208 MSM0655 1 COG1243 MSM0842 1 COG1255 Uncharacterized protein conserved in archaea MSM0894 2 COG1300 Uncharacterized membrane protein MSM0215, MSM1526 1 COG1303 Uncharacterized protein conserved in archaea MSM0932 1 COG1339 MSM1257 1 COG1359 Uncharacterized conserved protein MSM1378 1 COG1371 Uncharacterized conserved protein MSM0668 1 COG1379 Uncharacterized conserved protein MSM1129 1 COG1387 MSM0063 1 COG1415 Uncharacterized conserved protein MSM0931 1 COG1422 Predicted membrane protein MSM0736 1 COG1430 Uncharacterized conserved protein MSM1339 1 COG1460 Uncharacterized protein conserved in archaea MSM1376 1 COG1469 Uncharacterized conserved protein MSM1033 2 COG1474 MSM0671, MSM1264 1 COG1478 Uncharacterized conserved protein MSM0975 1 COG1511 Predicted membrane protein MSM0093 2 COG1520 FOG: WD40-like repeat MSM1247, MSM1567 1 COG1548 MSM0851 1 COG1578 Uncharacterized conserved protein MSM0551 1 COG1602 Uncharacterized conserved protein MSM0346 2 COG1617 Uncharacterized conserved protein MSM0348, MSM0349 1 COG1627 Uncharacterized protein conserved in archaea MSM0983 1 COG1630 Uncharacterized protein conserved in archaea MSM0123 1 COG1641 Uncharacterized conserved protein MSM0935 1 COG1665 Uncharacterized protein conserved in archaea MSM1058 1 COG1679 Uncharacterized conserved protein MSM1192 1 COG1685 MSM0835 1 COG1690 Uncharacterized conserved protein MSM0666 1 COG1693 Uncharacterized protein conserved in archaea MSM1417 1 COG1698 Uncharacterized protein conserved in archaea MSM1268 1 COG1701 Uncharacterized protein conserved in archaea MSM0140 2 COG1704 Uncharacterized conserved protein MSM0660, MSM1422 1 COG1710 Uncharacterized protein conserved in archaea MSM0069 1 COG1711 Uncharacterized protein conserved in archaea MSM1136 1 COG1714 Predicted membrane protein/domain MSM1493 1 COG1718 MSM0952 1 COG1720 Uncharacterized conserved protein MSM0132 2 COG1738 Uncharacterized conserved protein MSM0646, MSM1382 1 COG1739 Uncharacterized conserved protein MSM0186 1 COG1751 Uncharacterized conserved protein MSM0628 1 COG1771 Uncharacterized protein conserved in archaea MSM0070 1 COG1784 Predicted membrane protein MSM0599 1 COG1786 Uncharacterized conserved protein MSM1155 1 COG1795 Uncharacterized conserved protein MSM1213 1 COG1809 Uncharacterized conserved protein MSM0086 1 COG1817 Uncharacterized protein conserved in archaea MSM0106 2 COG1822 Predicted archaeal membrane protein MSM0581, MSM1216 1 COG1836 Predicted membrane protein MSM0659 1 COG1844 Uncharacterized protein conserved in archaea MSM0356 1 COG1849 Uncharacterized protein conserved in archaea MSM0614 2 COG1852 Uncharacterized conserved protein MSM0225, MSM0649 1 COG1860 Uncharacterized protein conserved in archaea MSM0285 1 COG1865 Uncharacterized conserved protein MSM0825 1 COG1872 Uncharacterized conserved protein MSM1603 4 COG1873 Uncharacterized conserved protein MSM0465, MSM0822, MSM0841, MSM1004 1 COG1891 Uncharacterized protein conserved in archaea MSM1628 1 COG1909 Uncharacterized protein conserved in archaea MSM0195 1 COG1915 Uncharacterized conserved protein MSM0875 1 COG1916 Uncharacterized homolog of PrgY (pheromone MSM1024 shutdown protein) 1 COG1917 Uncharacterized conserved protein, contains double- MSM1447 stranded beta-helix domain 1 COG1920 Uncharacterized conserved protein MSM0288 1 COG1937 Uncharacterized protein conserved in bacteria MSM0959 1 COG1944 Uncharacterized conserved protein MSM0480 1 COG1945 Uncharacterized conserved protein MSM0878 1 COG1950 Predicted membrane protein MSM1166 1 COG1971 Predicted membrane protein MSM0030 1 COG1990 Uncharacterized conserved protein MSM0605 1 COG1991 Uncharacterized conserved protein MSM0145 1 COG2029 Uncharacterized conserved protein MSM1057 1 COG2035 Predicted membrane protein MSM1582 1 COG2042 Uncharacterized conserved protein MSM0126 1 COG2043 Uncharacterized protein conserved in archaea MSM0115 1 COG2078 Uncharacterized conserved protein MSM0867 1 COG2090 Uncharacterized protein conserved in archaea MSM1591 1 COG2098 Uncharacterized protein conserved in archaea MSM0985 1 COG2106 Uncharacterized conserved protein MSM0763 1 COG2122 Uncharacterized conserved protein MSM0088 1 COG2136 MSM1632 2 COG2138 Uncharacterized conserved protein MSM1280, MSM1281 1 COG2246 Predicted membrane protein MSM1289 2 COG2314 Predicted membrane protein MSM0109, MSM1739 2 COG2364 Predicted membrane protein MSM0673, MSM0676 1 COG2429 Uncharacterized conserved protein MSM0973 1 COG2450 Uncharacterized conserved protein MSM0406 1 COG2456 Uncharacterized conserved protein MSM1624 1 COG2457 Uncharacterized conserved protein MSM0873 1 COG2892 Uncharacterized protein conserved in archaea MSM1633 1 COG3273 Uncharacterized conserved protein MSM1274 2 COG3274 Uncharacterized protein conserved in bacteria MSM1370, MSM1556 1 COG3356 Predicted membrane protein MSM0776 1 COG3367 Uncharacterized conserved protein MSM0407 1 COG3482 Uncharacterized conserved protein MSM0481 1 COG3543 Uncharacterized conserved protein MSM0430 3 COG3548 Predicted integral membrane protein MSM0468, MSM0469, MSM1205 1 COG3586 Uncharacterized conserved protein MSM1741 1 COG3815 Predicted membrane protein MSM1770 1 COG3874 Uncharacterized conserved protein MSM0683 1 COG3976 Uncharacterized protein conserved in bacteria MSM1637 1 COG4009 Uncharacterized protein conserved in archaea MSM0794 1 COG4010 Uncharacterized protein conserved in archaea MSM0793 1 COG4012 Uncharacterized protein conserved in archaea MSM1243 1 COG4014 Uncharacterized protein conserved in archaea MSM0840 1 COG4016 Uncharacterized protein conserved in archaea MSM0578 1 COG4017 Uncharacterized protein conserved in archaea MSM0575 1 COG4018 Uncharacterized protein conserved in archaea MSM0571 1 COG4019 Uncharacterized protein conserved in archaea MSM0574 1 COG4020 Uncharacterized protein conserved in archaea MSM1221 1 COG4021 Uncharacterized conserved protein MSM0463 1 COG4022 Uncharacterized protein conserved in archaea MSM0643 1 COG4029 Uncharacterized protein conserved in archaea MSM0812 1 COG4030 Uncharacterized protein conserved in archaea MSM0309 1 COG4033 Uncharacterized protein conserved in archaea MSM0103 1 COG4035 Predicted membrane protein MSM0315 1 COG4036 Predicted membrane protein MSM0320 1 COG4037 Predicted membrane protein MSM0321 1 COG4038 Predicted membrane protein MSM0322 1 COG4039 Predicted membrane protein MSM0323 1 COG4040 Predicted membrane protein MSM0324 1 COG4041 Predicted membrane protein MSM0325 1 COG4042 Predicted membrane protein MSM0326 2 COG4050 Uncharacterized protein conserved in archaea MSM0811, MSM1130 1 COG4051 Uncharacterized protein conserved in archaea MSM0809 1 COG4053 Uncharacterized protein conserved in archaea MSM0229 1 COG4065 Uncharacterized protein conserved in archaea MSM1006 2 COG4066 Uncharacterized protein conserved in archaea MSM0064, MSM0367 1 COG4068 Uncharacterized protein containing a Zn-ribbon MSM0417 1 COG4069 Uncharacterized protein conserved in archaea MSM0815 1 COG4071 Uncharacterized protein conserved in archaea MSM0630 1 COG4073 Uncharacterized protein conserved in archaea MSM0726 1 COG4077 Uncharacterized protein conserved in archaea MSM1034 1 COG4078 Predicted membrane protein MSM0319 1 COG4079 Uncharacterized protein conserved in archaea MSM1472 1 COG4081 Uncharacterized protein conserved in archaea MSM0104 1 COG4084 Uncharacterized protein conserved in archaea MSM0314 1 COG4121 Uncharacterized conserved protein MSM1555 1 COG4289 Uncharacterized protein conserved in bacteria MSM1302 1 COG4635 MSM1262 3 COG4713 Predicted membrane protein MSM0521, MSM1291, MSM1444 2 COG4744 Uncharacterized conserved protein MSM1402, MSM1719 1 COG4883 Uncharacterized protein conserved in archaea MSM1086 1 COG4907 Predicted membrane protein MSM1421 1 COG5015 Uncharacterized conserved protein MSM0863 1 COG5305 Predicted membrane protein MSM1288 1 COG5423 Predicted metal-binding protein MSM0050 1 COG5440 Uncharacterized conserved protein MSM1265 4 COG5464 Uncharacterized conserved protein MSM0067, MSM0681, MSM1765, MSM1785

TABLE 10 Glycosyltransferases (GT) in M. smithii strain PS and M. stadtmanae proteomes classified according to Carbohydrate Active enZyme (CAZy) database CAZy GT family Protein Annotation M. smithii GT1 MSM0423* glycosyltransferase (modular protein with two domains distantly related to glycosyltransferases), GT2/GT1 families [CAZy] GT2 MSM0423* glycosyltransferase (modular protein with two domains distantly related to glycosyltransferases), GT2/GT1 families [CAZy] MSM1290 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1294 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1297 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1310 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1311 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1312 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1316 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1321 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1323 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1324 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1328 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1329 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1330 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1503 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1507 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1545 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1594 glycosyltransferase (modular protein with two N-terminal beta- glycosyltransferaserelated domains and C-terminal glycerophosphotransferase-related domain), GT2 families [CAZy] MSM1602 glycosyltransferase (modular protein with N-terminal beta- glycosyltransferase-related domain and C-terminal glycerophosphotransferase-related domain), GT2 family [CAZy] MSM1623 glycosyltransferase (related to beta-glycosyltransferases), GT2 family [CAZy] MSM1627 glycosyltransferase (related to bactoprenol beta-glucosyltransferase), GT2 family [CAZy] GT4 MSM0836 related to alpha-glycosyltransferases, GT4 family [CAZy] MSM1313 distantly related to glycosyltransferases, GT4 family [CAZy] MSM1317 distantly related to glycosyltransferases, GT4 family [CAZy] MSM1322 distantly related to alpha-glycosyltransferases, GT4 family [CAZy] GT66 MSM0716 glycosyltransferase (distantly related to oligosaccharyltransferases), STT3 subunit, GT66 family [CAZy] M. stadtmanae GT1 Msp_0515 partially conserved hypothetical protein Msp_0645 predicted glycosyltransferase GT2 Msp_0042** predicted glycosyltransferase Msp_0045 predicted glycosyltransferase Msp_0054 predicted glycosyltransferase Msp_0203 predicted glycosyltransferase Msp_0206 predicted glycosyltransferase Msp_0207 predicted glycosyltransferase Msp_0212 predicted glycosyltransferase Msp_0215 predicted glycosyltransferase Msp_0218 predicted glycosyltransferase Msp_0220 predicted glycosyltransferase Msp_0441 predicted glycosyltransferase Msp_0442 predicted glycosyltransferase Msp_0492 predicted glycosyltransferase Msp_0493 predicted glycosyltransferase Msp_0495 predicted glycosyltransferase Msp_0496 predicted glycosyltransferase Msp_0500 predicted glycosyltransferase Msp_0538 predicted glycosyltransferase Msp_0541 predicted glycosyltransferase Msp_0645 predicted glycosyltransferase Msp_0989 predicted glycosyltransferase Msp_1087 predicted glycosyltransferase Msp_1481 conserved hypothetical membrane-spanning protein Msp_1540 partially conserved hypothetical protein GT4 Msp_0039 predicted glycosyltransferase Msp_0044 predicted glycosyltransferase Msp_0049 predicted glycosyltransferase Msp_0051 predicted glycosyltransferase Msp_0052 predicted glycosyltransferase Msp_0053 predicted glycosyltransferase Msp_0055 predicted glycosyltransferase Msp_0056 predicted glycosyltransferase Msp_0057 predicted glycosyltransferase Msp_0101 predicted glycosyltransferase Msp_0492 predicted glycosyltransferase Msp_0991 predicted glycosyltransferase GT66 Msp_0368 conserved hypothetical membrane-spanning protein *modular protein **probable fragment

TABLE 11 InterPro-based classification of adhesin-like proteins (ALPs) in the M. smithii strain PS and M. stadtmanae proteomes

¹Predictions completed using NetNGlyc and NetOglyc (htt://www.cbs.dtu.dk/services/). ²InterPro domains: Invasin/intimin cell-adhesion (IPR008964); Bacterial Ig-like (IPR003344); pectin lyase fold (IPRO11O5O); GAG lyase, Chondroitinase B-type (IPR012333); Polymorphic membrane protein, Chlamydia (IPR003368); Parallel beta-helix repeat (IPR006626); Peptidase S8 and S53 (IPR000209); Penicillin-binding protein, transpeptidase fold (IPR012338); Carboxypeptidase regulatory region (IPR008969)

TABLE 12 M. smithii GeneChip Genes Probe Average number of Naming Prefix Represented Probesets pairs probe pairs per probeset control sequences AFFX 64 64 1024 16 protein coding genes MSM 1778 2018 19967 11 tRNA genes (1-2 MSM-tRNAxx 34 74 450 11 probesets/gene) rRNA genes1 MSMxx-rRNA 8 7 77 11 intergenic sequences ig 1581 4931 3 ¹Note that the M. smithii genome contains three 5S rRNA genes, one 7S rRNA gene, two 16S rRNA genes, and two 23S rRNA genes. Due to the high nucleotide sequence identity among rRNA genes of a given type, each is represented by a single probeset (the 16S rRNA probeset is replicated four times on the GeneChip

TABLE 13 BLAST analysis of the putative M. smithii strain PS prophage Phage Protein M. smithii Protein Sequence ID* Function HMM Annotation Phage HMM E value MSM1640 5417 unknown Phage_integrase: Phage integrase family PF00589 2.30E−06 MSM1654 5721 Gp40 ERF: ERF superfamily PF04404 6.90E−11 MSM1671 5397 large terminase subunit psiM2_ORF9: phage uncharacterized protein, TIGR01630 0.0042 C-terminal domain MSM1672 5398 portal protein portal_PBSX: phage portal protein, PBSX TIGR01540 6.70E−12 family MSM1675 6246 putative structural protein MSM1677 6247 putative structural protein MSM1684 20206 ORF001 TMP: TMP repeat PF05017 0.0036 MSM1691 6262 PeiW *from the Phage Sequence Databank

TABLE 14 M. smithii strain PS treated with varying concentrations of statins Atorvastatin treated cells, average optical density (600 nm), standard deviation 1 mM 100 μM 10 μM methanol 0.032 (0.006) 0.032 (0.003)  0.03 (0.001) 0.032 (0.004) 0.018 (0.002) 0.032 (0.007) 0.042 (0.004)  0.07 (0.007) 0.001 (0.003) 0.031 (0.006)  0.09 (0.005) 0.135 (0.008) 0.001 (0.004)  0.03 (0.007) 0.079 (0.027)  0.13 (0.012) 0.008 (0.004) 0.033 (0.007) 0.139 (0.043) 0.234 (0.018) 0.007 (0.012) 0.033 (0.002) 0.233 (0.11) 0.195 (0.05) 0.001 (0.006) 0.024 (0.007) 0.115 (0.045) 0.218 (0.064) Pravastatin treated cells, average optical density (600 nm), standard deviation 1 mM 100 μM 10 μM ethanol 0.034 (0.003) 0.035 (0.003) 0.039 (0.004) 0.036 (0.005) 0.036 (0.006) 0.069 (0.02) 0.066 (0.003) 0.072 (0.012) 0.031 (0.003) 0.104 (0.03) 0.097 (0.025) 0.128 (0.011) 0.038 (0.003) 0.104 (0.024) 0.084 (0.009) 0.109 (0.011) 0.026 (0.006) 0.139 (0.078)  0.08 (0.014) 0.223 (0.015) 0.016 (0.01) 0.217 (0.175) 0.181 (0.048) 0.258 (0.105) 0.017 (0.004) 0.297 (0.111) 0.039 (0.015) 0.212 (0.113) Rosuvastatin treated cells, average optical density (600 nm), standard deviation 1 mM 100 μM 10 μM DMSO 0.031 (0.002) 0.031 (0.003) 0.034 (0.002) 0.033 (0.002) 0.024 (0.006) 0.026 (0.009) 0.068 (0.006) 0.075 (0.006) 0.017 (0.006) 0.021 (0.002) 0.101 (0.009) 0.125 (0.013)  0.03 (0.014)  0.02 (0.004) 0.082 (0.011) 0.093 (0.007) 0.013 (0.008) 0.027 (0.016) 0.122 (0.039) 0.152 (0.05) 0.018 (0.004) 0.033 (0.005) 0.159 (0.058) 0.117 (0.029) 0.003 (0.002) 0.033 (0.042) 0.174 (0.146) 0.183 (0.071)

TABLE 15 M. smithii strain F1 treated with varying concentrations of statins Atorvastatin treated cells, average optical density (600 nm), standard deviation 1 mM 100 μM 10 μM methanol 0.015 (0.006)  0.01 (0) 0.019 (0.001) 0.015 (0.003) 0.008 (0.014) 0.018 (0.001) 0.039 (0.004) 0.045 (0.003) 0.013 (0.01) 0.018 (0.002) 0.039 (0.007) 0.069 (0.002) 0.004 (0.014) 0.018 (0.003) 0.056 (0.011) 0.092 (0.003) 0.001 (0.011) 0.016 (0.002) 0.061 (0.023) 0.115 (0.008) 0.001 (0.015) 0.015 (0.001) 0.084 (0.033) 0.155 (0.019) Pravastatin treated cells, average optical density (600 nm), standard deviation 1 mM 100 μM 10 μ ethanol 0.011 (0.001) 0.007 (0.002) 0.019 (0.001) 0.017 (0.002) 0.022 (0.002) 0.047 (0.004)  0.05 (0.003)  0.05 (0.005) 0.026 (0.003) 0.066 (0.004) 0.071 (0.003) 0.073 (0.006) 0.026 (0.003) 0.085 (0.008) 0.102 (0.003) 0.095 (0.004) 0.022 (0.002) 0.089 (0.01) 0.124 (0.004) 0.121 (0.011) 0.018 (0.003) 0.133 (0.029) 0.168 (0.004) 0.153 (0.024) Rosuvastatin treated cells, average optical density (600 nm), standard deviation 1 mM 100 μM 10 μM DMSO 0.015 (0.003)  0.01 (0.003) 0.021 (0.003) 0.015 (0.003) 0.016 (0.003) 0.026 (0.003) 0.046 (0.004) 0.043 (0.001) 0.019 (0.003) 0.027 (0.004) 0.057 (0.002) 0.062 (0.003) 0.019 (0.003) 0.026 (0.004) 0.081 (0.008) 0.081 (0.005) 0.018 (0.003) 0.025 (0.001) 0.085 (0.021) 0.103 (0.005)  0.02 (0.006) 0.016 (0.003) 0.094 (0.048) 0.102 (0.017)

TABLE 16 M. smithii strain ALI treated with varying concentrations of statins Atorvastatin treated cells, average optical density (600 nm), standard deviation 1 mM 100 μM 10 μM methanol  0.01 (0.008) 0.015 (0.003) 0.012 (0.002) 0.019 (0.004) 0.016 (0.007) 0.008 (0.002) 0.026 (0.016) 0.043 (0.015) 0.052 (0.063) 0.002 (0.001) 0.058 (0.084) 0.046 (0.022) 0.018 (0.028) 0.014 (0.016) 0.072 (0.066) 0.074 (0.024) 0.025 (0.043) 0.008 (0.014) 0.031 (0.046)  0.06 (0.044)  0.01 (0.012) 0.001 (0) 0.024 (0.02) 0.093 (0.053) Pravastatin treated cells, average optical density (600 nm), standard deviation 1 mM 100 μM 10 μM ethanol 0.013 (0.002) 0.011 (0.003) 0.015 (0.001) 0.025 (0.009) 0.036 (0.045) 0.054 (0.036)  0.06 (0.027) 0.047 (0.012) 0.103 (0.176) 0.072 (0.076) 0.071 (0.037) 0.061 (0.026) 0.051 (0.027) 0.079 (0.122) 0.086 (0.048) 0.083 (0.036) 0.018 (0.026) 0.104 (0.154) 0.083 (0.053) 0.083 (0.038) 0.081 (0.032) 0.091 (0.143) 0.116 (0.05) 0.111 (0.047) Rosuvastatin treated cells, average optical density (600 nm), standard deviation 1 mM 100 μM 10 μM DMSO 0.017 (0.007) 0.029 (0.016) 0.019 (0.005) 0.014 (0.002) 0.032 (0.02) 0.033 (0.037) 0.044 (0.008)  0.04 (0.007)  0.02 (0.02) 0.012 (0.009) 0.038 (0.011) 0.044 (0.008) 0.013 (0.01) 0.028 (0.021) 0.056 (0.036) 0.058 (0.006) 0.015 (0.009) 0.015 (0.018) 0.074 (0.036) 0.085 (0.003) 0.016 (0.01) 0.015 (0.026)  0.1 (0.02) 0.126 (0.013)

TABLE 17 M. smithii strain B181 treated with varying concentrations of statins Atorvastatin treated cells, average optical density (600 nm), standard deviation 1 mM 100 μM 10 μM methanol 0.007 (0.004) 0.004 (0.001) 0.011 (0.001) 0.007 (0.003) 0.018 (0.001) 0.013 (0.003) 0.032 (0.007) 0.034 (0.006) 0.014 (0.003) 0.005 (0.002) 0.032 (0.006) 0.046 (0.022) 0.009 (0.002) 0.003 (0.005)  0.04 (0.008)  0.07 (0.029)  0.01 (0.004) 0.003 (0) 0.044 (0.011) 0.121 (0.027)  0.01 (0.003) 0.006 (0.001) 0.048 (0.009) 0.133 (0.026) Pravastatin treated cells, average optical density (600 nm), standard deviation 1 mM 100 μM 10 μM ethanol 0.007 (0.001) 0.003 (0.001) 0.011 (0.001) 0.009 (0.003) 0.019 (0.003) 0.039 (0.005) 0.047 (0.002) 0.039 (0.013) 0.015 (0.008) 0.061 (0.004) 0.061 (0.003) 0.048 (0.03) 0.014 (0.001) 0.088 (0.002) 0.102 (0.007) 0.094 (0.075) 0.016 (0.002) 0.114 (0.006) 0.135 (0.01) 0.137 (0.057) 0.015 (0.006) 0.171 (0.031) 0.198 (0.02)  0.14 (0.037) Rosuvastatin treated cells, average optical density (600 nm), standard deviation 1 mM 100 μM 10 μM DMSO  0.01 (0) 0.006 (0.006) 0.012 (0.002) 0.005 (0.004) 0.016 (0.004) 0.013 (0.003) 0.029 (0.001) 0.032 (0.003) 0.011 (0.002) 0.008 (0.001)  0.04 (0.001) 0.066 (0.02)  0.01 (0.005) 0.007 (0.003) 0.066 (0.005) 0.095 (0.018) 0.014 (0.004) 0.004 (0.002) 0.097 (0.014) 0.148 (0.032) 0.008 (0.003) 0.001 (0.002) 0.121 (0.012) 0.194 (0.073) 

1. An array comprising a substrate, the substrate having disposed thereon at least one nucleic acid, wherein the nucleic acid comprises a nucleic acid sequence selected from the nucleic acid sequences listed in Table A.
 2. The array of claim 1, wherein the nucleic acid or nucleic acids are located at a spatially defined address of the array.
 3. The array of claim 2, wherein the array has no more than 500 spatially defined addresses.
 4. The array of claim 2, wherein the array has at least 500 spatially defined addresses.
 5. A method of selecting a compound that has efficacy for modulating a gene product of M. smithii present in the gastrointestinal tract of a subject, the method comprising: a. comparing an M. smithii gene profile to a gene profile of the subject, b. identifying a gene product of the M. smithii gene profile that is divergent from a corresponding gene product of the subject gene profile, or absent in the gene profile of the subject, and c. selecting a compound that modulates the M. smithii gene product but does not substantially modulate the corresponding divergent gene product of the subject.
 6. The method of claim 5, wherein the compound inhibits the M. smithii gene product, but does not substantially inhibit the corresponding gene product of the subject.
 7. The method of claim 6, wherein the compound inhibits the growth of M. smithii.
 8. The method of claim 6, wherein the compound decreases the efficiency of carbohydrate metabolism in the subject.
 9. The method of claim 6, wherein the compound promotes weight loss.
 10. The method of claim 5, wherein the compound upregulates the M. smithii gene product, but does not substantially upregulate the corresponding gene product of the subject.
 11. The method of claim 10, wherein the compound promotes the growth of M. smithii.
 12. The method of claim 10, wherein the compound increases the efficiency of carbohydrate metabolism in the subject.
 13. The method of claim 10, wherein the compound promotes weight gain.
 14. The method of claim 5, wherein the compound, as administered to a subject, modulates the M. smithii gene product but does not substantially modulate the corresponding divergent gene product of the subject.
 15. The method of claim 14, wherein the compound is an HMG-CoA reductase inhibitor.
 16. A method for modulating a gene product of M. smithii present in the gastrointestinal tract of a subject, the method comprising administering to the subject an HMG-CoA reductase inhibitor that has been formulated for release in the distal portion of the subject's gastrointestinal tract and thereby substantially inhibits more of the HMG-CoA reductase of M. smithii compared to the subject's HMG-CoA reductase.
 17. The method of claim 16, wherein the inhibitor is a statin. 